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 detect neuronal nuclear antigens (= antineuronal nuclear antibodies ANNA), cytoplasmic antigens of Purkinje cells (= anti-Purkinje cell antibodies APCA), synaptic or retinal proteins (see Table 6). In most cases of paraneoplastic syndromes the detection of specific AAb can strongly suggest the presence of a tumor. Anti-Hu positive patients with paraneoplastic encephelomyelopathies (PEM) or subacute sensory neuronopathy (SSN) most often have small cell lung cancer (SCLC) as underlying disease. Similarly, anti-Yo positive patients with paraneoplastic cerebellar degeneration (PCD) often harbor gynaecological neoplasms. Furthermore, Hu, Yo and Ri AAb can be found in lower frequency and at lower titers in SCLC or ovarian cancer patients without neurological diseases [67, 68]. Neurological syndromes associated with AAb to ion channel proteins have a lower frequency of tumors as the syndromes associated with Hu, Yo and Ri antibodies. Patients with anti-VGKC positive acquired neuromyotonia have SCLC or thymoma in 20% and only 10-15% of the AchR antibody positive Myasthenia gravis (MG) cases are associated with thymoma. In thymoma associated MG other autoantigens such as ryanodine receptor and titin may also play a pathogenic role [69,70] (see also the chapter "Thymoma and Autoimmunity" by Y. Sherer and Y. Shoenfeld, this volume).


There is an association of many autoimmune diseases with malignancies and on the other hand of specific autoimmune phenomena in patients with hematological and epithelial neoplasms [35, 72] (see also the chapter "SLE and Cancer" by M. Abu-Shakra, D. Buskila and Y. Shoenfeld, this volume). The close relationship between autoimmunity and cancer may have several causes (reviewed in [35] and [73]): a common susceptibility (genetic and immunologic predispositions), the activation of oncogenes and abnormal expression of oncoproteins, defects in apoptotic processes or common pathogenic factors inducing the diseases. Therefore, due to a possible common background, some disease-specific AAb may also be detectable in cancer patients without or before the development of autoimmune disease. Indeed, several AAb (antinuclear antibodies of various specificities, rheumatoid

Table 6. Autoantibodies against onconeural antigens and associated diseases [62-71 ]

Autoantibodies Onconeural antigens

Paraneoplastic syndromes

Associated tumors

Anti-Hu Hu antigens

Anti-Ri Ri antigens

Anti-Yo Yo antigens

Paraneoplastic encephalomyelopathies (PEM) Subacute sensory neuronopathy (SSN)

Opsoclonus/myoclonus syndrome (OMS)

Paraneoplastic cerebellar degeneration (PCD)

Antiamphiphysin Synaptic vesicle-related protein amphiphysin Paraneoplastic stiff man syndrome (SMS)

Paraneoplastic encephalomyelitis




Antititin Anti-RyR


Protein(s) of the P/Q, N and L type of voltage-gated calcium channels (VGCC)

Lambert-Eaton myasthenic syndrome (LEMS)

Protein(s) of voltage-gated potassium channels Acquired neuromyotonia (Isaacs' syndrome)

Protein(s) of the acetylcholine receptor Myasthenia gravis (MG)

Cross-reactive titin epitopes Ryanodine receptor

Recovering a protein of photoreceptor cells Cancer-associated retinopathy

Small cell lung cancer

Breast cancer Small cell lung cancer

Ovarian cancer Breast cancer Small cell lung cancer Hodgkin's lymphoma

Breast cancer Small cell lung cancer

Small cell lung cancer

Small cell lung cancer thymoma

Thymoma or thymic carcinoma

Breast cancer Small cell lung cancer factor, antiphospholipid antibodies, antibodies against various tissues) have been detected in sera of tumor patients (reviewed in [35]). However, two studies including comparative groups of age-adjusted healthy subjects had shown that the increased incidence of RF, anticardiolipin antibodies, ANA as well as the ANA specificities against DNA, histones, Ro/SS-A, La/SS-B, Sm and Ul-RNP in sera of tumor patients may well reflect the higher age of these patients rather than be a result of the tumor itself [74,75], Further studies with larger groups of patients and with the inclusion of other AAb specificities should be done to clarify whether there is any specific relationship between defined AAb and cancer. In CTD the strongest associations to epithelial malignancies are in the group of patients with dermatomyositis, polymyositis and systemic sclerosis (reviewed in [35]; see also the chapter "Scleroderma and Cancer" by L. Guillevin). Furthermore, the results of Boyeldieu et al. [76], Kuwana [77] and Zuber [78] have led to the supposition that there is a relationship between systemic sclerosis (SSc) typical AAb and cancer. We addressed this question with a retrospective study on uranium miners—a risk group for both SSc and cancer [79, 80].

Nonorgan specific AAb were screened by indirect immunofluorescence on HEp-2 cells in sera of 1743 uranium miners [81], including sera of 73 uranium miners with lung cancer, 30 miners with radiograph-ically suspected lung cancer and 25 miners with other malignant tumors. In ANA positive cases sera were analyzed for CTD typical AAb against dsDNA (CLIFT, ELISAs), Sm, Ul-RNP, Ro/SS-A, La/SS-B, topoi-somerase I (immunodiffusion, ELISAs, immunoblot) and CENP-B (ELISA). Results were regarded as positive only if they were at least middle titred in one ELISA and positive in at least another but different assay. Antinucleolar antibodies were assessed as positive with patterns like those of SSc typical nucleolar antibodies (antifibrillarin, -RNA-polymerases, -Pm-Scl, -To) at titer > 1:320. We compared the results of the cancer patients without CTD symptoms (all cancers and separately lung cancer) with the results of the following groups of miners or control subjects:

Table 7. CTD typical autoantibodies in sera of different groups of uranium miners

Group of uranium miners or control subjects


Autoantibodies (in %) against

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