The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.

OBJETIVOS: Determinar a frequência do fator reumatoide (FR-IgM), anticorpos antipeptídeos citrulinados cíclicos (anti-CCP), antinucleares (AAN), anticitoplasma de neutrófilos (ANCA), anticardiolipina (aCL) e anti-β2 glicoproteína I (anti-β2GPI) em pacientes com hanseníase, com e sem comprometimento articular, avaliando a possível associação entre estes autoanticorpos e as manifestações articulares, a forma clínica, a reação hansênica, o tratamento com poliquimioterapia (PQT) e a alta. PACIENTES E MÉTODOS: 158 pacientes com hanseníase foram distribuídos em dois grupos; 73 pacientes com (Grupo I) e 82 sem comprometimento articular (Grupo II). Compuseram o Grupo III 129 indivíduos saudáveis. MÉTODOS: aglutinação com partículas de látex para FR-IgM, imunofluorescência indireta para AAN e ANCA, e, ELISA para anti-CCP, aCL e anti-β2GPI. RESULTADOS: Dentre 158 pacientes com hanseníase, 56 apresentavam a forma virchowiana (VV). A frequência de anticorpos anti-CCP, FR e AAN nos Grupos I e II foi semelhante à do Grupo III. ANCA não foi detectado em nenhum dos grupos. Anticorpos aCL foram mais frequentes nos pacientes com hanseníase (Grupos I e II) que em controles sadios (15,8% vs. 3,1%; P < 0,001), não sendo observada diferença entre Grupos I e II (P = 0,67). Anticorpos anti-β2GPI também foram mais frequentes nos pacientes que nos controles (46,2% vs. 9,4; P < 0,001), sem diferença significativa entre os Grupos I e II. Houve predomínio do isotipo IgM com relação ao IgG tanto para aCL (88% vs. 16%, P = 0,001), quanto para anti-β2GPI (97,3% vs. 12,3%, P < 0,001). Nenhum paciente apresentou manifestações sugestivas de trombose vascular. CONCLUSÃO: A frequência de anticorpos aCL e anti-β2GPI foi significativamente maior nos pacientes com hanseníase que nos controles saudáveis. Entretanto, a positividade dos demais autoanticorpos foi semelhante à dos controles. Não foi observada associação entre autoanticorpos e comprometimento articular, episódios reacionais, tratamento com PQT ou alta, nem com a forma clínica da hanseníase, exceto para anticorpos aCL que foram mais frequentes na forma clínica VV.

OBJECTIVE: Determine the frequency of rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein I antibodies (anti-β2GPI) in leprosy patients, with and without joint involvement, and to evaluate the possible association among those antibodies and articular manifestations, clinical type, reactional episodes, polychemotherapic treatment (PCT), and discharge from PCT. PATIENTS AND METHODS: One hundred and fifty-eight leprosy patients were divided in two groups of 73 patients (Group I) and 82 patients (Group II). Group III was composed of 129 healthy individuals. Methods: Semi-quantitative latex agglutination test for IgM-RF, indirect immunofluorescence for ANA and ANCA, and ELISA for anti-CCP, aCL, and anti-β2GPI. RESULTS: Fifty-six (35.4%) of 158 leprosy patients had lepromatous leprosy (LL). The frequency of anti-CCP, RF, and ANA antibodies in Groups I and II was similar to that of Group III. Antineutrophil cytoplasmic antibodies were not detected in any patient. Anticardiolipin antibodies were more frequent in leprosy patients (Groups I and II) than in control group (15.8% vs. 3.1%; P < 0.001), and differences between Groups I and II (P = 0.67) were not observed. Anti-β2GPI antibodies were also more common in leprosy patients than in control group (46.2% vs. 9.4%; P < 0.001), without differences between Groups I and II. A predominance of IgM isotype over IgG isotype was observed both for aCL (88% vs. 16%; P = 0.001) and anti-β2GPI (97.3% vs. 12.3%; P < 0.001). Patients did not present manifestations suggestive of vascular thrombosis. CONCLUSION: The frequency of aCL and anti-β2GPI antibodies was significantly increased in leprosy patients than in healthy individuals. However, positivity to other autoantibodies was similar to that observed in the control group. An association between autoantibodies and joint involvement, reactional episodes, polychemotherapic treatment, discharge, and clinical type of leprosy was not observed, except for aCL antibodies, which were more frequent in lepromatous leprosy.

The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at _20°C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3%, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4% of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2% and IgM RF in 62.3%. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.

Cajal bodies (CB) are ubiquitous nuclear structures involved in the biogenesis of small nuclear ribonucleoproteins and show narrow association with the nucleolus. To identify possible relationships between CB and the nucleolus, the localization of coilin, a marker of CB, and of a set of nucleolar proteins was investigated in cultured PtK2 cells undergoing micronucleation. Nocodazol-induced micronucleated cells were examined by double indirect immunofluorescence with antibodies against coilin, fibrillarin, NOR-90/hUBF, RNA polymerase I, PM/Scl, and To/Th. Cells were imaged on a BioRad 1024-UV confocal system attached to a Zeiss Axiovert 100 microscope. Since PtK2 cells possess only one nucleolus organizer region, micronucleated cells presented only one or two micronuclei containing nucleolus. By confocal microscopy we showed that in most micronuclei lacking a typical nucleolus a variable number of round structures were stained by antibodies against fibrillarin, NOR-90/hUBF protein, and coilin. These bodies were regarded as CB-like structures and were not stained by anti-PM/Scl and anti-To/Th antibodies. Anti-RNA polymerase I antibodies also reacted with CB-like structures in some micronuclei lacking nucleolus. The demonstration that a set of proteins involved in RNA/RNP biogenesis, namely coilin, fibrillarin, NOR-90/hUBF, and RNA polymerase I gather in CB-like structures present in nucleoli-devoid micronuclei may contribute to shed some light into the understanding of CB function.