Info

The new lymphotropic herpesviruses (HHV-6, HHV-7, HHV-8) and hepatitis C 23. virus (HCV) in human lymphoproliferative diseases an overview. Haematologica 1996 81 265-281. 11. Gaidano G, Pastore C, Gloghini A, Capello D, Polito P, Vaccher E, et al. Human herpesvirus type-8 (HHV- 24. 8) in haematopoietic neoplasia. Leuk Lymphoma 1997 24(3-4) 257-266. 12. Humphreys SR, Holley KE, Smith LH, Mc Ibrat DC. Mesenteric angiofollicular lymph node hyperpla- 25. sia (lymphoid...

T Cellmediated Antitumor Immunity

Due to their pronounced capacity to prime T cells DC are considered as optimal tools to enhance insufficient T-cell responses against tumors. To initiate a specific cellular defence against tumors, tumor cells must be found wherever they are located in the body and must be recognized by tumor-reactive T lymphocytes, especially by CTL. The frequency of tumor-specific CTL is usually extremely low and there is little evidence that antitumor immunity is efficiently induced in tumor-bearing hosts...

Introduction

Numerous autoimmune phenomena have been reported in malignancies. These autoimmune conditions may be regarded as paraneoplastic syndromes or syndromes that cannot be explained by the local effects of the tumor or its metastases. The most common neoplasm associated with autoimmune diseases is thymoma. Thymoma is an epithelial tumor that constitutes approximately 15 of all mediastinal masses 1 , It has a wide spectrum of aggressiveness, varying from showing slow progression with a relatively...

References

Human lymphocyte subsets in health and disease. In Yamamura T, Tada T, eds., Progress in Immunology. Tokyo Academic Press, 1984 1047-1051. 2. Calligaris-Cappio F, Gobbi M, Bofill M, Janossy G. Infrequent normal B lymphocytes express features of B chronic lymphocytic leukemia. J Exp Med 1982 155 623-628. 3. Youinou P, MacKenzie L, Lamour A, Mageed RA, Lydyard PM. Human CD5-positive B cells in lymphoid malignancy and connective tissue diseases. Eur J Clin Invest 1993 23 139-150. 4....

Classification Of Tumor Antigens Recognized By T Cells

The identification of antigens recognized by tumor-reactive T cells was a cornerstone in tumor immunology. It has provided the opportunity to develop new and effective anticancer therapies 37 , Three different approaches were pursued in order to identify the antigenic peptides presented by MHC class I molecules to tumor-specific CTL. The first method is based on the transfection of recombinant DNA libraries into cells expressing the respective allelic MHC molecule. The transfected cells are...

Association Of Hsp 70 And Gp96 With Immunogenic Peptide Antigens In Cells

Recently, several studies provided direct evidence that immunogenicity of stress protein preparations is due to bound peptides. Arnold et al. 60 showed that only gp96 preparations from TAP competent cells can induce CTL responses against antigens, whose presentation is TAP-dependent. In conclusion, gp96 can associate with CTL-recognized peptide antigens translocated by TAP. Further studies showed that the depletion of peptides from tumor-derived HSP 70 preparations abrogated their...

Conclusion

It seems reasonably clear that combination chemotherapy may be associated with rheumatic manifestations. On the one hand, this may consist of a relatively self-limiting condition characterized by arthralgia and myalgia with negative autoimmune serology and this has been given the name postchemotherapy rheumatism. On the other hand, there may be a rare subgroup of patients who develop an autoimmune connective tissue disease following combination chemotherapy which may represent another facet of...

Antigen Presentation By Dendritic Cells

For the generation of a T cell response by DC in secondary lymphoid organs peptide fragments are presented in association with molecules of the major histocompatibility complex (MHC). For activation of CD8+ cytotoxic T cells (CTL), DC have to present antigenic peptides complexed to MHC class I molecules. The majority of class I-presented peptides are generated by degradation of cytoplasmic proteins by a multicatalytic proteolytic unit, the pro-teasome 13-15 . Dedicated peptides produced in the...

B

Figure 1. (A) The structure HLA-DRa promoter. The W, XI, X2, Y boxes are bolded and boxed. The octamer, which is unique to the HLA-DRa promoter is boxed. The TATA box is only bolded. The consensus sequences within the boxes are underlined the S box within the W box, the CCAAT box within the Y box. (B) The binding of transcription factors to the HLA-DRa promoter. The three complexes primarily regulating HLA-DRa expression are the RFX complex, which binds to the XI box and may also bind to the W...

Concluding Remarks

Experiments and clinical trials over the past few years have given telltale signals that there might be an operational window of specificity through which antitumor immunity can be triggered against tumor-associated self-antigens without concomitant or subsequent induction of autotoxicity. Further studies need to be done to address this issue both at the experimental and, in due course, at the clinical level. Nonetheless, the risk of inducing damage to normal tissues remains a major concern in...

New Approach To Identifying Informative Autoantibodies Associated With Lung Cancer

Recently, construction of tumor cell cDNA libraries and screening using autologous host sera (SEREX) has revealed that a B-cell response to tumor antigens is more prevalent than previously observed 28-32 , The success of this methodology is likely attributable to enriching for cDNA expressed by the autologous tumor. This enrichment no doubt facilitates the identification and cloning of antigens corresponding to autoantibodies in the autologous sera, which may be relatively rare or nonexistent...

Cutaneous TCell Lymphoma

Immunological disorders frequently occur in patients with cutaneous T-cell lymphoma and include monoclonal gammopathy, haemolytic anaemia, cold agglutinins, acquired factor VII inhibitor, warm and cold erythrocyte antibodies and plasma cell myeloma. Mycosis Fungoides characterised by a clonal proliferation of CD4 and CDW29 positive cells, may be associated with B-cell proliferation and the production of a variety of antibodies, including those directed against phospholipids. Clinically the...

Historical Perspective

The association between SS and lymphoma has been known since 1951, when Rothman et al. 6 described the first case of this association. Some years later, in 1964, Talal and Bunim 7 reported the first study on the incidence of lymphoma in a cohort of 58 patients with SS followed-up over 4 years and observed 3 cases of reticulosarcoma and 1 of IgM macroglobulinemia. In 1966, Hornbakeret al. 8 described the association of SS and nodular reticulum cell sarcoma in a patient dying due to a severe...

Germline Abnormalities

Monoclonal gammopathy is an uncommon finding, accounting for 1.2 of randomly selected hospitalized patients, 3 in patients older than 70 years and 10 of patients over 80 years. Significance is determined by the magnitude of serum monoclonal protein and associated findings of M-protein in the urine, lytic lesions, anemia, hypercalcemia, renal failure and disease progression. Bernett reported a retrospective study of 534 cases in which the referring diagnosis was plasmacytoma. Twenty-two patients...

Epidemiology

Malignancies of various types may be associated with thromboses and it has recently become clear that a proportion of patients who suffer from malignancy-associated thrombosis have elevated aPL. The clinical association of cancer with thrombosis was first documented over 100 years ago by Trousseau 4 . The work of Bowie and his colleagues from the Mayo Clinic in the 1970s stressed the high prevalence of overt or subclinical intravascular coagulation in cancer patients 5, 6 and recent reviews...

Prognosis

Predictive Factors for Lymphoma Development Lymphoma is an extraglandular complication whose early diagnosis in patients with SS has high priority. Knowing that patients with SS are at higher risk of developing lymphoma, several investigators have attempted to establish predictive factors for this progression (Table 7). In 1978, Kassan et al. 15 were the first to show prospectively that lymphadenopathy, splenomegaly, parotid gland enlargement and previous exposure to cytotoxic agents are...

Hi

Intracerebral inoculation of JC virus in newborn Golden Syrian hamsters induces neural origin tumors. Eighty percent of newborn hamsters inoculated with JC virus succumb to neural origin neoplasms. The most prevalent, medulloblastoma, appears as a highly cellular, poorly differentiated tumor with evidence of high mitotic activity. Note the presence of neuroblastic (Homer Wright) rosettes. Original magnification, x400. toma. This tumor was also PCR positive for the Mad-4 strain of JCV....

Mhc Ii

Microvasculitis 85 MIgs 62,66, 67,71 Minimal change glomerulopathy 121 Mitochondrial antigens 5 Mitosin 176 Mixed cryoglobulinemia syndrome 285, 287, 289 Monoclonal gammopathy 98, 143, 223, 262, 269 Monoclonal paraproteins 23 Monocytoid B-cell lymphomas (MBCL) 58, 63, 64, 65

Factors Responsible for Bcell Clonal Expansion

Chromosomal translocations are the most common genetic alterations associated with B-cell lymphomagenesis. These changes are responsible for the functional alteration of a variety of genes contributing to B-cell transformation, including proto-oncogenes and genes encoding the proteins involved in the control of the cell cycle, differentiation and programmed cell death. Of interest is the fact that at least one specific chromosomal abnormality characterizes each lymphoma subtype. These findings...

Natural History

Few prospective studies have been performed in primary SS and, consequently, the natural history is poorly understood. The evidence obtained in cross-sectional studies suggests that multiple etiologic factors are involved and that the pathogenesis of this disorder is a multistage process fundamentally involving immunological mechanisms. Moreover, it is assumed that when progression occurs it is a slow process, clinically characterized by gradually increasing symptoms and signs. Within the...

Induction Of Autoimmunity By

In some experimental models, T-cells recognizing stress protein epitopes, especially from HSP 60, can induce autoimmune disease 9, 73 . Stress protein HSP 60 is a dominant epitope in T-cell responses to certain pathogens, for example mycobacteria 7478 . Since stress proteins are highly conserved with sequence homologies between bacterial and human members of stress protein families, it has been discussed that bacterial infections can trigger autoimmune disease 9, 10, 73, 79 . Recent...

Mcs 287

Melanoma 24, 94, 99, 141, 143, 145, 216, 270, 271, 357, 382-384, 398,400, 401,431 Membranous nephropathy 121 Mesotheliomas 122 Metastases 133, 187 Methotremate 34 Methotrexate 19, 23, 26, 34, 432 Methylchloranthrene 397 M gammopathies 33 MGUS 98 MHC 4, 89, 187, 215, 217, 224, 344, 354-356, 397, 416, 425 MHC class I 218, 238, 353, 379, 381, 388 MHC class II 234, 317-322, 324-327, 347, 355

Summary

Idiotypes and anti-idiotypes are becoming widely used in various experimental applications in multiple fields of research. Administration of anti-idiotypes has been attempted in order to manipulate immune reactions affecting autoimmune diseases. Immunization with anti-idiotypes and idiotypes may change the autoantibody expression in autoimmune diseases. However, in certain experimental models administration of antiidiotypes and idiotypes may even propagate the induction of autoimmune-like...

Preface

To some people, the study of cancer and autoimmunity may be something only slightly less sterile than a Johnson & Johnson gauze pad, a pursuit followed by dilettanti and pseudo-scholastic professors. To others, the word connotates the exotic, the esoteric and the desirable. To us, it embodies the hopes and ambitions of generating an anti-tumor response in the patient. It is somewhat ironic that over forty years ago there were two disciplines that started with TI. There was tumor immunology...

Selection Of Target Antigens For Antitumor Vaccination

As outlined above, tumor antigens that might serve as potential targets of antigen-specific cancer vaccines are being defined in several cancers. The optimal development of these vaccines requires identification of the most potent rejection antigens. One of the criteria to be considered in selecting antigens for antitumor vaccination is the precursor frequency of antigen-specific tumor-reactive T cells, since the frequency of T cells reactive with particular tumor antigens would bear great...

Serum

Enhancement by a booster with cultured human melanoma cells of the anti-HMW-MAA immune response triggered by mouse anti-id mAb MK2-23. Rabbits 97-6 and 97-7 were immunized on day 0, 14, 28 and 42 with KLH conjugated mouse anti-id mAb MK2-23 mixed with Freund's adjuvant and on day 56 with irradiated, cultured human melanoma cells Colo 38 (2 x 106). Pre -immune serum (O) and serum harvested on day 49 (A) did not show any reactivity with Colo 38 melanoma cells in a binding assay (left...

Nihh

ETS2 and ERGB FLI1 expression correlates with SLE activity. ERGB FLI1, ETS2 and ETS1 mRNA expression was studied by quantitative RT-PCR in PBMC samples from SLE patients with very active (lanes 1 and 2), active (lanes 3, 4 and 5) and inactive (lanes 6 and 7) disease compared to that of a healthy individual (lane 8). Expected size of PCR products are shown on the right side (further details are described in ref. 42 ). DBA 2 normal mice. As shown in Fig. 3, ERGB FLI 1 expression did not...

Mucocutaneous Paraneoplastic Syndrome

Mucocutaneous paraneoplastic syndromes represent a group of dermatoses of variable pathology, morphology and etiology. These syndromes either precede, occur concurrently or follow the existence of an internal malignancy. The suggested mechanisms involved in the pathogenesis of these syndromes include 13 (1) production of tumor substances which cause the dermatosis (2) depletion of a specific substance by the tumor that can cause the dermatologie symptoms and (3) a host response to the neoplasm...

Tumorassociated Antigens Selfaltered Selfparadigm

A body of data over the past few years have determined that the immune repertoire of cancer patients contains both B and T cells that recognize antigens expressed by autologous cancer cells. Thus, tolerance to human cancer does not effectively delete the immune repertoire against cancer cells. The known universe of immunogenic antigens, defined by structure and function, on human cancers is still small, but is expanding rapidly 25, 26 , The human immune system seems to recognize antigens...

The Case Of Acquired Resistance To Autoimmune Disease

Among the various systems of experimentally induced autoimmune disease (AID), EAE (Experimental Allergic Encephalomyelitis) is a prime example for this discussion. Some strains of rats and mice, if immunized with myelin basic protein (MBP), one of myelin proteins, in Complete Freunds Adjuvant, develop a severe disease caused by inflammation in the central nervous system, consequent to the activation of CD4 T cells. Disease can be induced also by transfer of purified MBP-specific CD4 T cells, if...

Usa

INSERM Unit 430 H pital Broussais 96, Rue Didot 75014 Paris Cedex 14 France University di Roma La Sapienza Rheumatic Disease Unit Department of Medicine 'B' Soroka Medical Center and Faculty of Health Science Division of Rheumatology Allergy and Clinical Immunology University of California at Davis TB 192, School of Medicine Davis, CA 95616-8660 USA Department of Microbiology and Molecular Genetics Loma Linda University School of Medicine Loma Linda, CA 922350 USA Unitat de Malalties...

Paraneoplastic Syndromes Of The Nervous System

Paraneoplastic syndromes of the nervous system are rare and affect less than 1 of cancer patients. These disorders often precede the identification of the underlying neoplasm and have a subacute onset. They can affect all parts of the nervous system usually causing focal neurological dysfunction with neuronal degeneration. The best current hypothesis that explains the peculiar phenomenon of nervous system degeneration in these syndromes is autoimmunity. Most investigations suggest that antigens...

Pss And Lung Carcinoma

Pulmonary involvement in PSS is characterized by fibrosis of the lung, a condition that does not, normally, cause hemoptysis. Therefore, the manifestation of hemoptysis in a patient with PSS and lung involvement should not go unchecked. It is usually the presentation of a secondary lesion that is possibly malignant. In 1953, the first report of an association between scleroderma and malignancy 2 described three patients, each with long- standing systemic sclerosis (PSS) and lung involvement. In...

Monitoring Of Cancer Patients

As yet, only a few studies (Table 1) focused on the fate of p53AAb in the follow-up of tumor patients. In 1994, Angelopoulou et al. 60 monitored five patients with ovarian cancer and one with breast cancer and showed that temporal changes of p53AAb correlated with disease progression or regression. The authors concluded that this immunization represents a continous process driven by the tumor and is not a temporally isolated event. In a later report on another breast cancer patient,...

The Influence Of Cigarette Smoke On The Effectors Of The Immune System

Cigarette smoke has been, and is, a major risk factor for lung carcinoma, cardiovascular disease and chronic obstructive lung disease (reviewed in ref. 9 . Although, the entire spectrum of effects of cigarette smoking on the immune system are not fully realized, it appears that smoking influences nearly any cellular component. Growing evidence implicates immune mechanisms in the breakdown of the normal pulmonary architecture in smokers, with the subsequent replacement of the alveolar cells by...

The Molecular Basis For The Regulation Of Mhc Class Ii Expression In Thyrocytes

Only few studies have looked at the different levels of regulation of MHC class II gene expression in thyroid cells, although the phenomenon of MHC class II induction in autoimmune and malignant diseases is very well documented, as has been described before. In IFN-y-induced macrophages the stability of MHC class II mRNA indicated long-lived transcripts. In contrast, in three different malignant thyroid cell lines the half-life value of HLA-DRa mRNA was measured between 1.3-7 h 63 , This...

Other Tissue Autoantibodies

Several workers reported increased incidence of smooth muscle antibodies of the IgG or IgM type in malignancies 32, 34, 37 . These autoantibodies were described in several malignant tumors including melanoma 52 , carcinoma of the lung 32 , breast 37 , ovary, lung 34 and cervix 32 , In one study 37 the presence of antismooth muscle antibodies was correlated with poor prognosis in patients with breast cancer. Since antismooth muscle antibodies typically are raised in chronic active hepatitis it...

Lymphoid Malignancies

Human CLL is a malignancy of the CD5+ B cells, characterized by the accumulation of mature appearing, long-lived, slow-growing CD5+ B cells in peripheral blood. Leukemia cells from approximately 95 of CLL patients co-express CD5 and other B-cell markers 24 . Thus, in most cases of CLL, there is a proliferation of B-cell clones characterized by low amounts of surface immunoglobulins and the presence of the CD5 molecule. There is no definite correlation between the expression of CD5 and surface...

The Cancerogenicity Of Cya Experience From Other Immunemediated Diseases

Being effective in the modulation and prevention of experimental autoimmune uveitis 87 , the use of CyA for the treatment of human uveitis has been spreading over the last decade. Guidelines for an optimal use of CyA in noninfectious endogenous uveitis are available 88 where a maximal dose of 5 mg Kg die is suggested. In the same report, among the side effects described in 339 patients with endogenous intermediate and posterior uveitis in 15 different clinical studies, no malignancies are...

Conclusions And Future Directions

The use of alloBMT and autoBMT for the treatment of otherwise resistant hematologic malignancies and and certain chemotherapy sensitive solid tumors, respectively, is well established. Our recent observations suggest that GVL and possibly GVT effects may be amplified with alloCT mediated by donor alloreactive lymphocytes which could be further activated with rIL-2. Furthermore, we suggest that equally effective GVL and possibly GVT effects may be induced with a safer alloBMT procedure following...

Malignancies Occurring During

Case reports suggest that the development of the two diseases is not coincidental and that scleroderma patients have twice the risk of developing malignancies than the general population. Lung and perhaps breast cancers seem to be more frequent in PSS patients. In a Danish series of 344 patients 7 , scleroderma was responsible for a 3-fold increased risk of death (Table 1). Most patients died of PSS-related causes (acute renal crisis, hypertension, lung fibrosis, etc.), but malignancies were...

Combination Chemotherapy

Recently, our unit has observed 6 patients with haema-tological malignancy (5 had a lymphoma and 1 had acute myeloid leukaemia) who developed an autoimmune connective tissue disease following combination chemotherapy 24 , Three patients developed SLE and 1 each developed lupus profundus, limited cutaneous systemic sclerosis and Churg-Strauss syndrome. Only 1 of these patients received interferon-a and his SLE developed 5 years after this therapy. These connective tissue diseases manifested...

Naa Clones Are Frequently Committed To Malignant Transformation

Accumulated evidence indicates that this autoreactive B-cell repertoire frequently undergoes a malignant transformation. This evidence arose from the study of monoclonal immunoglobulins (MIg), chronic lymphocytic leukemia (CLL) and follicular non-Hodgkin lymphomas (FNHL). MIg correspond to normal synthetic products whose counterpart can be found in the heterogenous normal Ig compartment. The antibody-like activity of MIg has been described against a large number of antigens, e.g., bacterial...

Antitumor Immunity And Autoimmune Disease

It is becoming increasingly accepted that a large set of antigenic determinants of the self have not induced self-tolerance 99 , and that a number of these peptide determinants furnish target structures for immune responses directed against tumors. As illustrated by the results of the hunt for tumor-associated antigens in recent years, tumors do not express mysterious nonself- or neoself-antigens, but rather a set of genes that are part of the self altered self-repertoire. In fact, the aberrant...

Detection Of A Malignant Disease

From all the reports on p53 autoantibodies it seems to come up that p53 autoantibodies are in general associated with a malignant disease, whereas, healthy blood donors are rarely positive for p53 autoantibodies. Two individuals were found to express p53 autoantibodies although no tumor was detected. Both individuals were heavy smokers and diagnosed for chronic cough or a benign obstructive tracheal tumor. Both developed lung cancer within 5 or 15 months, respectively 27 . In a study of...

Adverse Effects Of Chemotherapy And Rheumatic Symptoms

A number of antineoplastic agents are known to have adverse effects that might mimic a rheumatic disease. For example, Raynaud's phenomenon is well described in association with cisplatin, vinblastine and bleomycin 10 , and more recently 5-fluorouracil may cause digital ischaemia 11 , Furthermore, bleomycin is also associated with the development of scleroderma 12, 13 . The cutaneous lesions seen in these patients treated with bleomycin are indistinguishable from idiopathic scleroderma where...

Nuclear Antigens As Candidates For Oncogenic Proteins

In a growing number of reports, antibodies present in the sera of cancer patients have provided useful mole cular tools for the identification of the corresponding antigens 27-32 . These autoantigens are often either mutated or overexpressed in tumors 32 , which strongly supports the idea that the immune response is indeed targeted against the tumor. Many of these autoantigens appear to be specific to an individual patient 33 , However, we hypothesize that the proteins involved in tumorigenesis...

The Use Of alloBmt For The Treatment Of Cancer

Allogeneic blood or marrow transplantation is the most effective modality to date to eradicate hematologic malignancies in patients at high risk to relapse or resistant to conventional doses of chemoradiother-apy. A standard autoBMT as well as alloBMT appear most suitable in patients with hematologic malignancies and solid tumors sensitive to chemoradiotherapy, since the rescue procedure enables administration of higher than conventional doses of cytoreductive antitumor agents. Following...

P53 Autoantibodies and Cancer Speciiicity Diagnosis and Monitoring

Flammann1 and Hella-Monika Kuhn2 1 Institute of Immunology, Pathology and Molecular Biology, Hamburg, Germany 2 Israelitic Hospital, Hamburg, Germany p53 has been rightfully called the guardian of the genome 1 , This tumor suppressor gene plays a critical cellular role with major implications in clinical oncology (for a review, see 2 ). In brief, its protein participates in the regulation of the cell-cycle, acts as transcriptional transactivator repressor, helps in DNA repair,...

Aps Associated With Immunotherapy

Immunotherapy using interleukin-2 (IL-2), ainterferon or both, for patients with melanoma may induce increased levels of antithyroid microsomal and antithyroglobulin antibodies which may persist for months 104-106 as well as the induction of other autoantibodies 107 , Becker et al. 108 reported that immunotherapy in patients with cancer may be associated with the induction of aPL. Thirty melanoma patients were studied and 2 out of 4 treated with -interferon alone (50 ) and 3 out of 8 (37.5 )...

Nyeso1

MAGE-1 antibodies were found in 1 out of 127 melanoma patients, 1 out of 32 ovarian cancer and 1 out of 24 lung cancer patients 60 SSX2 antibodies were found in patients with melanoma, in 2 out of 11 using a plaque assay and in 1 of 127 using ELISA 9, 60 NY-ESO-1 were found in 12 out of 127 melanoma patients, 4 out of 32 ovarian cancer, 2 out of 26 breast cancer and 1 out of 24 lung cancer patients 60 response causing paraneoplastic syndromes affecting the nervous system. AAb against ONA may...

Musculoskeletal Symptoms

Many forms of malignancy are associated with musculoskeletal symptoms and these may be due to direct infiltration of bones, joints or muscles. Paraneoplastic syndromes may also involve the musculoskeletal system and several chapters in this book have already dealt with these phenomena. In the last 5 years, it has been noted that musculoskeletal symptoms may develop following combination chemotherapy for various malignancies, particularly breast cancer. Most of these patients were otherwise...

Suggestions On Strategies To Break Dominant Tolerance To Cancer Cells

How can we then achieve effective anti-tumor immunity, while avoiding the risk of emergence of autoimmune diseases The experimental protocols, which make normal animals suffer from autoimmune disease, seem to give us a clue to approach the problem. It has been shown that treatment of normal adult animals with cyclophosphamide (Cy) or sublethal y-irradiation, if coupled with thymectomy, results in development of various organ-specific autoimmune disease, whereas each treatment alone does not...

CyA in Systemic Lupus Erythematosus

Some evidence suggest that patient with systemic lupus erythematosus (SLE) have a higher incidence of malignancy, especially hematopoietic 63-65 , breast, lung, and gynecological cancers 66,67 even if not all reports agree with this observation 68, 69 . None of the available lupus cohort studies have demonstrated a clear correlation between immunosuppression and higher cancer risk, but there is a reasonable concern of a possible increased risk with the additional exposure to immunosuppressive...

Hsp 65

Human papilloma virus (HPV) 36, 265, 268, 269, 355, 399 Human T-cell leukemia virus (HTLV) type 1 36, 183, 187, 194 Hypertrichosis lanugiosa acquisita 126 Hypertrophic osteoarthropathy 125, 134, 136 Hypothyroidism 280, 288, 312, 401, 413 Idiopathic thrombocytopenic purpura (ITP) 5, 141, 236, 413 Idiotype 8, 9, 224-227, 233, 365, 380, 398 IgA 182, 194, 261,264-271 IgA autoantibodies 267 IgA deficient 262 IgA dermatosis 271 IgA nephropathy 121 IgG2-IgG4 deficiency 262 IgM 56 IgMk 62, 68 IgMk...

Immune Response And Gestational Trophoblastic Disease

Tumors are analogous to tissue graft in that they are most likely recognized by the immune system, yet through either a tolerance or evasion mechanism, do not elicit a destructive immune response. Clinical evidence shows that individuals with suppressed immune systems are most susceptible to tumor appearance. However, animal experimentation indicates that immune surveillance is directed toward viruses rather than tumors. Because tumors do appear and grow within a host, they must somehow evade...

In Vivo Antiidiotypic Therapy In Autoimmune Diseases

Anti-idiotypic therapy has not been tried in human autoimmune diseases directly. One study used the approach of passage of plasma over an anti-idiotype column which removes antibodies bearing the common idiotype 51 , In this study, an anti-3I Id column was used to remove anti-ds DNA antibodies bearing the 31 Id from patients with SLE. There were no significant side effects. The recent development of 'humanized' murine or rat monoclonal antibodies opens the way for direct injection of Id-bearing...

Molecular Analyses for BCell Clonality

The evaluation of clonal B-cell expansion is an important preliminary step to better investigate the patho-biologic events implicated in the different stages of progression and in different microenvironments. The assessment of clonality may be dependent on the technique used to identify monoclonal B-cell proliferation in tissue lymphoid infiltrates, and includes immunophenotypic and immunogenotypic analysis 83 , 7.2.1. Immunophenotypic analysis Clonal expansions are characterized by identical...

Peripheral TCell Lymphoma PTCL

This term includes heterogenous diseases such an-gioimmunoblastic T-cell lymphoma, angiocentric lymphoma, intestinal T-cell lymphoma and adult T-cell lymphoma leukaemia. The majority however are grouped in a category termed peripheral T-cell lymphoma, unspecified. These latter lymphomas usually affect adults with generalised disease and may involve extranodal sites. The clinical course is often aggressive with frequent relapses 85, 86 , A 65-year-old man with a history of hypertension and...

Cd And Autoimmunity

Although the pathogenic mechanism of CD is not yet fully elucidated, there is no doubt about the involvement of immune factors in the development of the disease. Many features present in CD fulfil the criteria generally accepted to define autoimmune disease and suggest that CD belongs to this group of diseases 1,11 (1) HLA linkage For the majority of patients, a particular HLA-DQ heterodimer, encoded by the DQA1 0501 and DQB1 0201 alleles on chromosome 6, confers the primary susceptibility to...

Role Of Ets In Cancer And Disease

The oncogene v-ETS was originally discovered as a fused component of a chimeric genome in an avian leukosis virus, E26 (a replication-defective retrovirus that arose by transducing portions of two chicken cellular proto-oncogenes, myb and ETS1. The E26 oncogene transforms fibroblasts, myeloblasts, and ery-throblasts in vitro and causes mixed erythroid-myeloid and lymphoid leukemia in vivo 3,4 , Malignant transformation by leukemia retroviruses can also result from proviral integration upstream...

Autoimmunity To Cenpf In Cancer

Although the clinical significance of anti-CENP-F autoantibodies still needs to be further investigated, the available evidence indicates that autoimmunity to this protein is likely to be associated with the presence of a malignant tumor. An evaluation of the clinical histories of 26 patients producing anti-CENP-F IgG antibodies revealed that 14 (54 ) of these patients had cancers of various types 20 , Some of the non-cancer patients had conditions associated with ab- normal or increased cell...

Ectopic ACTH Syndrome

A wide range of tumors has been described to produce biologically active ACTH. Many studies have shown that the molecular mechanism of this syndrome is due mainly to a precursor of the ACTH molecule which is proopiomelanocortin POMC and is a 31 kD glycoprotein. These precursor molecules, which are produced normally by the normal cells, are produced by some tumors in greater concentrations. Some tumors convert these precursors to biologically active ACTH, thus causing this paraneoplastic...

Mhc Class Ii Expression On Autoimmune And Malignant Thyroid Cells

Regulatory Effects of IFN-y and TNF-a Many investigators have used the thyroid gland as a model for research of autoimmune processes. Autoimmune thyroid diseases are the archetype of organ specific autoimmune disorders, and shares with them T-cell dependency as a common characteristic. Inappropriate MHC class II expression has been first observed on thyroid cells derived from patients with Graves' autoimmune thyroid disease 40 , and lead to the hypothesis that such expression would result...

Small Bowel

Diffuse plasma cell infiltration of the small intestine is geographically unique, and correlates with socioeconomic status. Diagnostic possibilities include re active plasma cell infiltration or neoplastic processes. Multiple theories have been proposed for this occurrence and revolve around continual antigen challenge with chronic parasitic infestations or exposure to luminal pathogens, then subsequent neoplastic terminal differentaion. Diffuse plasmacytic infiltration or small intestine...

Iga Gastrointestinal Cancer

Recently, the association of gastric carcinoma and H. pylori has been proposed by several epidemiological studies 30, 31 , These studies correlate the immunoglobulin responses to H. pylori with the incidence of gastric carcinoma. The predominant antibody response was IgG, however, the occurrence of IgA positive and IgG negative serology accounts for about 2 of patient responses 32 , In a large study from Finland, increased IgA and low pepsinogen levels were significantly associated with...

Castlemans Disease and Autoimmunity

Valesini Universit di Roma La Sapienza , Italy Castleman's disease CD is an uncommon lympho-proliferative disorder of unknown aetiology first described by Castleman 1 in 1954. CD histopathologic classification is complex and this disease is also referred to as giant lymph-node hyperplasia, an-giomautous lymphoblastoid hamartoma and follicular lymphoreticuloma 2 , Although CD is a distinct clin-icopathology entity, it tends to frequently share some common...

Iga And Other Neoplasms

Humoral responses in patients with colorectal, esophageal, gastric, lung, fallopian tube, endometrial, endocervical, breast, ovarian, prostatic carcinomas, and mixed colorectal polyps have been intensively evaluated Table 2 . Tsavaris et al. 69 studied 100 patients with colorectal carcinoma. Three samples were evaluated before therapy and every 2 months post-therapy. Patients with increased levels of IgG and IgM had a longer interval for cancer progression. Multiple factors asso ciated with 57...

The Effect Of Thymectomy On Autoimmune Diseases

Bone-marrow transplantation has recently been suggested as an optional treatment for severe autoimmune diseases 25 , As there is a strong association between thymic pathology and autoimmunity, it is not surprising that thymectomy also might have a beneficial effect on the course of autoimmune diseases. 4.1. The Rationale Behind Thymectomy for the Treatment of Autoimmune Diseases Since MG is the autoimmune disease most commonly found in patients with thymoma, literature reports focus on the...

Iga Deficiency And Neoplasia

The association of immunodeficiency disease and the development of malignancy is based on observational data. Cunningham-Rundles et al. 10 screened the sera of 4120 patients at Memorial Sloan Kettering Cancer Center and showed that in 1517 sera from pa tients with lymphoproliferative disorders, 6 were IgA deficient, frequency 1 253 and in 249 sera from patients with gastrointestinal neoplasm, 2 were IgA deficient frequency 1 125 . The incidence of IgA deficiency at their institution was 1 273,...

Response

The principal role of the immune system is to confer protection on the organism against foreign invading pathogens, which can gain access to the body by different routes. The targeted specific immune response is generated by the combined interaction of the cellular and humoral responses, both coordinated by the production of active substances the cytokines. Cellular immunity refers to the immune mechanisms mediated by T lymphocytes, regardless of immunoglobulin molecules, whereas humoral...

Haematological Leukemia

Patients with solid tumours exhibiting positive aPL have been sporadically reported and they include carcinoma of the lung 45, 46 kidney 47, 48 , colon 49 , prostate 50 , liver 51 , ovary 52 , trachea 53 as well as thymoma 54 . The 2 patients reported with lung carcinoma 4546 had differing clinical aPL-associated complications. The first had elevated titres of aCL IgG isotype and suffered recurrent DVT and pulmonary embolism resistant to anticoagulation with warfarin as well as SC heparin....

Autoimmune Diseases

Cal tumor manifestation or diagnostic detection. This has been shown in 7 of the 39 patients whose serum samples were available. In 4 patients only response A could be seen. In one patient response B and in two patients response C was detected 41,24 and 25 months before disease manifestation. Furthermore, we found a significantly higher frequency of p53 AAb in uranium miners compared with blood donors p 0.008 . Taken together, there are important hints of a predictive value of p53 AAb regarding...

Mechanisms Of Immunogenicity Of Tumor Stress Protein Preparations

As stated above, in the current model for the mechanism of gp96-induced tumor-specific immunity gp96-peptide complexes are processed by professional phagocytic APC and gp96-associated peptides are channelled into the MHC-class I restricted antigen presentation pathway. This model was corroborated by cell depletion experiments which showed that for the priming phase of gp96-induced immunity CD8 positive T cells and phagocytic cells are needed 51 and by representation of gp96-associated peptide...

Functional Significance Of

OVEREXPRESSION OF ERGB FLI1 GENE IN AUTOIMMUNE DISEASE Lymphocytes are important components and regulators of immune response. We and have shown that the ETS family of proteins are involved in lymphoid cell development, differentiation, maturation and activation and therefore, they are important regulators of lymphoid gene expression. Inappropriate expression of ETS family of genes may have a detrimental effect on lymphoid cell differentiation, activation and function. T cells in autoimmune...

Malignancies Occurring Several Years After Onset Of The Vasculitis

Rinaldi et al. 20 studied 41 patients with cirrhosis alone, and 41 patients with cirrhosis and hepatocellular carcinoma. They showed that patients with cirrhosis are at high risk of developing hepatocellular carcinoma, especially when they have hepatitis B or C virus infection. They also demonstrated a strong association between hepatitis C virus infection and cryoglobulinemia in cirrhosis patients with and without hepatocellular carcinoma. Cryoglobulins were detected in 88 of patients with...

Iga And Head And Neck Cancer

Head and neck cancers are primarily squamous cell carcinomas that arise from the mucosal epithelial cells of the head and neck. They include tumors of the paranasal sinuses, nasopharynx, oropharynx, hy-popharynx, larynx and the oral cavity. A variety of immunological abnormalities occur in tumors and may be important prognostically. Both cell-mediated and humoral immunity is altered in cancers, although attention has been more focused on the humoral immune system in mucosal tumors of the head...

Hypercalcemia Syndrome

Hypercalcemia is a relatively common manifestation in cancer present in up to 40 of patients, depending on the type of tumor 3 . The cause of hypercalcemia is a cancer-produced substance which has some PTH activities. This protein has been termed PTH-related protein PTH-RP , and is a 141-amino acid protein homologous with PTH in its amino terminus 6 . The PTH-RP gene is located on the short arm of chromosome 12 and has been shown to be expressed at low levels in many normal tissues, such as...

Pss And Breast Cancer

An additional type of malignancy frequently reported with PSS is breast carcinoma. Several cases are cited where the two diseases developed within months of one another 10-12 , In a 1979 study 1 , an even greater incidence of breast carcinoma in association with PSS than lung carcinoma was found. Occasionally, a worsening of the scleroderma was noted when the malignancy recurred, while improvement of skin changes occurred after treatment of the neoplasm 10 . A similar finding was also noted in...

Iga And Cervical Cancer

Cervical carcinoma has been one of the most common causes of cancer related death in women for many years. Although the mortality rates have fallen by 50 in the last three decades in developed countries, it continues to be a major gynecologic cancer in the underdeveloped countries. There were 15,700 new cases of invasive cervical cancer and 4900 deaths in 1996 46 , Lower socioeconomic status, early age of sexual activity, multiple sexual partners and smoking are considered to be predisposing...

Nonhodgkin Lymphoma Eatl Enteropathyassociated Tcell Lymphoma

Coeliac patients have a higher incidence of non-Hodgkin's lymphoma than that of the general population 7, 34-39 , Malignancy develops in 8-13 of patients. EATL is slightly more frequent in males and has its peak in the sixth decade of life. An interesting recent finding shows that the incidence of lymphoma in CD diagnosed in elderly patients over 60 years was much higher 23 than that in younger population 8 . Moreover, other autoimmune diseases, dermatitis herpetiformis and autoimmune...

Monoclonal Selection

Physiologically, humoral immune response to an antigen involves the activation of several B-cell clones producing immunoglobulins with different heavy and light chains. Studies carried out in animal models as well as in humans have shown that the appearance of B-cell clonality may occur in the context of a preexisting polyclonal lymphocyte proliferation, probably induced by continuous exposure to either autoantigens favored by altered self-tolerance or exogenous antigens such as those...

Causality

In 1965, Sir Austin Bradford-Hill published his famous postulates in The Environment and Disease Association or Causation 40 , The nine Bradford-Hill's postulates summarized in Table 6 give a mea sure of the degree in which evidence of causality between a factor and a disease could be established. The Bradford-Hill's postulates result particularly suitable to evaluate the degree in which an autoimmune rheumatic disease is conditioning a higher probability to develop a malignant neoplasm. Table...

Autoimmune Diseases In Benign And Malignant Thymoma

Malignant thymomas, as opposed to benign thymomas, constitute a minority of all epithelial tumors of the thymus. These are classified into type I tumors which are locally invasive, tend to recur and occasionally metastasize widely, but cannot be differentiated cytologically from their benign counterparts 21 and type II tumors that are also identified as thymic carcinoma since they exhibit cytological and histological features of malignancy identical to carcinomas arising in extrathymic sites 22...

Autoimmune Diseases Associated With Thymoma

The various autoimmune diseases that occur in patients with thymoma include mainly myasthenia gravis MG , pemphigus, systemic lupus erythematosus SLE , pure red cell aplasia PRCA , and other conditions that seldom appear concomitantly with this tumor. MG is an autoimmune disease resulting from the production of antibodies against the acetylcholine receptor of the muscular endplate 4 , Only about one-third of the patients with thymoma have MG, while 10-15 of myasthenic patients have a thymoma....

The Autoreactive Repertoire Is An Important Component Of The Normal Bcell Repertoire

In 1956, Witebsky and Rose 9 induced for the first time, an experimental autoimmune disease mediated by autoantibodies autoimmune thyroiditis. They succeeded in inducing the disease by injecting thyroglob-ulin in the presence of Freund's adjuvant. Since they were able to produce autoantibodies, the precursor B cells producing these should exist. More recently, considerable data have accumulated raising doubts concerning the clonal deletion theory as an unique explanation for tolerance since 1...

The Ets Gene Family

Transcription factors are critical for proper regulation of cellular proliferation, differentiation and programmed cell death. Alterations in transcription factor function have been shown to cause developmental defects or carcinogenesis. ETS family of transcription factor genes have been isolated and characterized from different organisms, including the human, mouse, rat, chicken, Xenopus, sea urchin, Drosophila and C. ele-gans reviewed in 3-7 . To date, over 30 members of the ETS family have...

Monoclonal Gammopathies

In this situation, a monoclonal protein is present in serum M protein . This is an immunoglobulin which persists constantly at an elevated level over many years without the development of any malignant systemic disease. It is caused by the proliferation of a single clone of mature differentiated B lymphocytes producing this y-globulin. This monoclonal immunoglobulin may not only be directed against proteins of the coagulation pathway usually factor VIII but may also be an antibody against the...

Hematological Paraneoplastic Syndrome

Cancer may affect the cellular elements of the blood as well as the coagulation system, resulting in a wide range of paraneoplastic syndromes Table 3 . In modern health-care systems routine hematological testing is so common that many cancers are first detected by one of these paraneoplastic syndromes. Anemia Anemia of cancer is probably the most common paraneoplastic syndrome 18 . It is usually characterized by a normochromic or mild hypochromic red blood cell RBC morphology with low serum...

Myeloma

Myeloma patients are predisposed to thrombosis because of a number of factors which include immobilisation, hyperviscosity, low grade DIC and possibly hypercalcaemia 1 . To this list must also be added the aPL. Myeloma is one of the B-cell disorders characterised by significant paraprotein production and most of the associated haemostatic abnormalities act to increase the risk of clinically significant bleeding rather than thrombosis 102 , 7.1. Plasma Cell Dyscrasias Multiple Myeloma Among 10...

Hypoglycemia Syndromes

The most common neoplasms associated with hypoglycemia are tumors of mesenchymal origin, such as mesotheliomas, fibrosarcomas, neurofibromas, spindle cell carcinomas and leiomyosarcomas. The most common mechanism involved in hypoglycemia is abnormal production of a precursor molecule to insulinlike growth factor IGF II, which is bound to insulin and IGF receptors, thus causing suppression of growth hormone secretion 8 . Other rare causes that are not well documented are the production of...

List of Contributors

Department of Medicine 'B' amp 'D' Soroka Medical Center and Ben-Gurion University Department of Immunology and Rheumatology Institute Nacional De La Nutricion Salvador Zubiran Mexico City Mexico University di Roma La Sapienza Department of Medicine 'B' Research Unit of Autoimmune Diseases Chaim Sheba Medical Center Affiliated to Tel-Aviv University Tel-Hashomer 52621 Israel University of Cape Town School of Medicine INSERM Unit 430 H pital Broussais 96, Rue Didot 75014 Paris Cedex 14 France...

Diagnosis 71 Detection of MIgs

MIgs represent the unique product of a single clone of relatively mature B lymphocytes or plasma cells. The presence of an MIg does not in itself demonstrate the existence of a malignant B-cell lymphoproliferative disorder and only indicates the presence of one or more clonal population s of B cells able to produce a homogeneous immunoglobulin. Screening for MIgs is commonly performed by serum protein electrophoresis on cellulose acetate or agarose gel, that in the majority of cases allows the...

Evolution Of The Autoimmunity Concept

Paul Ehrlich was the first to coin the term autoimmunity 11 with regard to the harmful aspects of immunity, namely the emergence of autoantibodies directed against the organism's own antigens. However, the expression used 'horror autotoxicus' has served to denote a mechanism avoiding autoimmunization, exemplified in goat models producing alloantibodies but not autoantibodies . The revolutionary ideas expressed by Ehrlich were subsequently abandoned for a century although anecdotal works...

Natural Autoimmunity

The existence of B and T-cells harboring self-reactivity complicates the concept of autoimmunity, since it goes to show that this property is not necessarily associated with disease states 18 . Moreover, the abundant existence of anti-self reactivity implies that representation of self within the immune system might even have teleological roles in terms of protection or immune modulation. As such, it has been initially proposed by Grabar 19 that natural autoantibodies NAA could act as...