Info

186p/172c 122

28/p

104p/130c

94p/188c

70p/72c t IgA G, HPV E2 t IgA HPV E2 t IgA w/cervical dysplasia t IgA 83% cervical t IgA 75% IEN t IgA cervical CA HPV- 16VPL

t IgA cervical 16 cervical secretions t IgA1M to E7 HPV 16 t IgA E2 protein CIN t IgA before

Serum & cervical IgA to EBV Persistent HPV

HPV 16 infection J, w/ CA of the cervix 4. w/ therapy patient with multiple myeloma in whom immunohis-tologic studies demonstrated high titer IgA binding with human endoneurium. IgA immunoblot reactivity was demonstrated with 58,43 and 8 kDa endoneurium components. Hays et al. reported the occurrence of breast cancer, IgA paraprotein and amyotrophic lateral sclerosis. All findings were verified at autopsy. Immunofluorescent studies demonstrated significant binding to axons and perikarya of nerve cells in the CNS and peripheral nervous system. The IgA antibody specifically reacted to a 200 kDa neurofilament protein [103], Cross-reactivity was demonstrated to surface components of neuroblastoma cells. Similar IgA reactivity has been demonstrated in neurodegenerative disorders not related to malignancy [104], A similar peripheral sensorimotor polyneuropathy has been reported in chronic myelomonocytic leukemia [105]. IgA is also associated with leukocytoclastic vasculitis, Henoch-Schonlein purpura/polyarteritis nodosa overlap syndrome, dermatitis herpetiformis and antilipid antibody [106-109].

POEMS syndrome or polyneuropathy, osteolytic lesions, scleroderma like lesions, diffuse adenopathy, and hepatosplenomegaly, has been associated with an IgA-A plasmacytoma [110], Approximately five cases of a scleroderma like illness have been reported as paraneoplastic syndromes, one IgA mediated and a second IgA with scleroderma and acanthosis nigra-cans [111]. The Crow-Fukase syndrome or progressive sensory neuropathy, generalized pigmentation of the skin, pretibial edema and gynecomastia, has been reported with an IgA-A extra medullary plasmacytoma [112].

Primary IgA nephropathy has been linked to cutaneous T-cell lymphoma [113, 114]. Mak et al. [115] reported a case with simultaneous onset of crescen-tic IgA nephropathy and gastrointestinal, low-grade B-cell lymphoma of the mucosa associated lymphoid tissue type (MALT), with kidney involvement. After treatment with chlorambucil the proteinuria and impaired creatinine clearance resolved. This also coincided with complete resolution of gastric and renal lymphoma infiltration. The close association of the onset and successful outcome of the two entities suggests a pathophysiological relationship between the MALT lymphoma and human IgA nephropathy. Sessa et al. [116] reported the association of IgA mesangial nephropathy and renal cell carcinoma. Tanaka et al. [117] reported IgA glomerulonephritis with renal cell carcinoma. Ito et al. [118] described mesangial lesions secondary to IgA and severe nephrotic syndrome associated with B-cell lymphoma. Glomerulonephritis secondary to IgA has been associated with a baseloid squamous cell carcinoma [119].

In malignant melanoma, vitiligo and melanoma with hypopigmentation, humoral responses to tyrosinase are demonstrable. This enzyme participates in pigment formation in melanocytes. The autoreactiv-ity is believed to be responsible for the melanoma with hypopigmentation syndrome. The antibody is primarily IgG and the highest titer is found in patients with vitiligo. In 4 out of 41 patients with malignant melanoma, the immunoglobulin type was IgA, with one type IgM. The subsequent clinical course for these patients was not reported. In melanoma and melanoma with hypopigmentation, specific antityrosinase reac tivity is an autoimmune, paraneoplastic reaction [120, 121],

Mucocutaneous disorders (cicatroid pimpagoid, linear IgA disease), paraneoplastic syndromes and long term topical medication use represent a spectrum of potentially blinding diseases [122], Of these diseases IgA multiple myeloma may be complicated by subcorneal pustular dermatosis [123]. Seven cases have been reported, of which five were associated with IgA paraproteinemia and IgA intra-epidermal deposits

[124]. Unusual bullous cutaneous IgA mediated lesions have been associated with lung cancer. Antibody activity to desmocollins I and II were demonstrated

[125], This autoantibody and those of linear IgA disease are directed to the proteins that comprise the hemidesmosome basment membrane complex [126], Linear IgA dermatosis is a bullous disease characterized by linear deposition of IgA at the basement membrane. McEvoy and Connolly [127] described two cases of linear IgA dermatosis with malignancy. One patient had plasmacytoma, which presented 2 months before linear IgA dermatosis. The other patient had chronic lymphatic leukemia diagnosed 1 year before the diagnosis of linear IgA dermatosis. There have been other cases of linear IgA malignancy including carcinoma of bladder, malignant melanoma [108], esophageal carcinoma [128], and Hodgkin's disease [119, 129]. The relationship of linear IgA dermatosis and malignancy are based on these observations. However, the temporal relationship between the occurrence of neoplasm and the onset of skin lesions has been variable. In the cases reported by Vignon et al. [130] and Barnadas et al. [129], the diagnosis of lymphoma and IgA dermatosis was made at the same time [130, 129]. In the cases described by Leonard et al. [108], the mean time between onset of dermatosis and symptoms of neoplasia was 60 months. In the cases reported by McEvoy and Connolly [127], the diagnosis of neoplasm was made after 2 months in one case and 12 months in another. In the case described by Sekula et al. [131], the patient had a blistering skin lesion 6 weeks after the diagnosis of transitional cell carcinoma of the bladder. The interval between carcinoma occurring after dermatosis in Kienzler et al.'s [132] case report was 5 years, and in Green et al.'s [128] case report was 7 years. The response of IgA dermatosis to chemotherapy of the associated malignancy is not well known. In Barnadas et al.'s [129] case, the bullous eruption responded to treatment of lymphoma and a flare of linear IgA dermatosis helped in the diagnosis of recurrent lymphoma. In Sekula et al.'s [131] patient with transitional cell carcinoma of the bladder and linear IgA dermatosis, both diseases responded to chemotherapy. In the case of Hodgkin's disease and IgA reported by Vignon et al. [130], the patient required treatment with dapsone after successful treatment of Hodgkin's disease. Of the two cases reported by McEvoy and Connolly [127], one had plasmacytoma which responded to radiation, while the dermatosis responded to prednisone and dapsone. In the second patient, with chronic lymphatic leukemia, the patient's skin disease recurred despite treatment. Given the large variety of tumors, disparity in clinical course, and temporal association, there appears to be a correlation with IgA linear dermatosis and neoplasia.

It appears that IgA and anti-IgA antibodies can be helpful in the diagnosis and prognosis of some neoplasms.

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