Absence of cross-reactivity to myeloperoxidase of anti-thyroid microsomal antibodies in patients with autoimmune thyroid diseases.

BACKGROUND: Thyroperoxidase is the major antigen of the thyroid microsomal antibodies (TMA) detected in autoimmune thyroid diseases. Its amino acid sequence has 44% homology with myeloperoxidase (MPO), an enzyme present in the primary granules of neutrophils and one of the major antineutrophil cytoplasmic antibodies (ANCA) antigens. The objective of the present study was to investigate the presence of cross-reactivity to MPO of TMA. METHODS: We studied sera from 51 patients with autoimmune thyroid diseases, all of them TMA-positive. The presence of ANCA was investigated by indirect immunofluorescence and by capture enzyme-linked immunosorbent assay. RESULTS: ANCA were positive in 3.9% of the TMA-positive sera and none of them reacted with MPO. In contrast, the ANCA-positive sera revealed antielastase activity. None of the ANCA-positive cases presented clinical signs of vasculitis. However, these 2 patients had been on prolonged treatment with propylthiouracil. CONCLUSIONS: We conclude that there is no cross-reactivity to MPO of TMA in patients with autoimmune thyroid diseases, possibly because of difference in the spatial configuration of the immunodominant region. The presence of ANCA in patients with autoimmune thyroid diseases without evidence of vasculitis might result from propyIthiouracil-induced polyclonal activation.

Anti-neutrophil cytoplasmic antibodies (ANCA) in the clinical forms of leprosy.

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies against enzymes present in primary granules of neutrophils and lysosomes of monocytes detected in systemic vasculitis and in other diseases, including infections. ANCA are markers of active Wegener granulomatosis, which presents some anatomo-pathologic and immune response features similar to those of leprosy. Thus, we raised the hypothesis that ANCA may be present in leprosy as markers specifically linked to the presence of vasculitis. The aim of this study was to determine the presence of ANCA in leprosy and its correlation with the clinical forms of the disease. Sera from 60 normal individuals and from 59 patients with different clinical forms of leprosy were studied. The patients were also allocated into reactional and nonreactional groups. By indirect immunofluorescence, ANCA were positive, an atypical pattern (A-ANCA), in 28.8% of the patient sera. A-ANCA predominated, although not significantly (p > 0.05), in the reactional groups 37.9% vs 20.0%), and in those at the lepromatous pole (41.6% vs 20.0%). There was no correlation between ANCA positivity and either disease duration, disease activity, or therapeutic regimen (p > 0.05). An interesting finding was the correlation between ANCA and gender: 94.1% of ANCA-positive patients were males (p < 0.01), a feature that so far has not been reported in ANCA-related diseases and for which there is no explanation at the moment. By ELISA, the sera of the lepromatous leprosy patients did not show activity against either PR3, MPO, HLE, the most common ANCA antigens. Because A-ANCA are nonspecific, this finding requires further investigation for the determination of the responsible antigen(s). In conclusion, A-ANCA are present in 28.8% of leprosy patients but are not related to vasculitis in the erythema nodosum leprosum reaction and are not a marker of a specific clinical form.

Human syngamosis. Two cases of chronic cough caused by Mammomonogamus laryngeus.

Parasites of the genus Mammomonogamus may occasionally affect the human respiratory tract, causing human syngamosis. We describe two cases of chronic unproductive cough caused by Mammomonogamus laryngeus that occurred in the state of São Paulo, Brazil. Some aspects related to human parasitism, diagnostic approach, and treatment are discussed.

Morphological basis of pulmonary edema in mice with cytokine-induced vascular leak syndrome.

Patients injected systemically with recombinant human interleukin-2 (rhIL-2) for treatment of solid tumor develop a vascular leak syndrome (VLS), characterized mainly by pulmonary edema whose pathogenesis is unknown. We have examined the structure of pulmonary vessels in mice with severe VLS induced by systemic injections of rhIL-2 and recombinant human interferon-alpha-A/D (rhIFN-alpha), which has a synergistic effect with IL-2. The pulmonary edema was associated with lesions of venous and capillary endothelia, alveolar basement membrane, and type I epithelial cells. These changes were more severe and diffuse than those seen in mice systemically injected with rhIL-2 alone, and in beige mice (deficient in NK cells and certain enzymes of polymorphonuclear leukocytes) injected with rhIL-2 and rhIFN-alpha. The endothelial lesions were comparable to those seen when leukocytes activated by cytokines react with activated endothelial cells in vitro, or at the site of injection of cytokines in vivo. The observations are in agreement with the interpretation that the severe lesions occurring in mice systemically injected with rhIL-2 with rhIFN-alpha result from the interaction of leukocytes with the endothelium. The results confirm the validity of previous studies performed in vitro or in animals injected intradermally with cytokines and extend their significance.