RESUMO
CD38 is a transmembrane protein expressed in B lymphocytes, and is able to induce responses as proliferation, differentiation or apoptosis. Several reports propose that CD38 deficiency accelerates autoimmune processes in murine models of autoimmune diabetes, lymphoproliferation and rheumatoid arthritis. Other reports have shown elevated CD38 expression in B and T cells from patients with autoimmunity; however, the role of CD38 is still unclear in the development of autoimmunity. Recently, it has been characterized as CD1dhi CD5+ regulatory B cell subpopulation able to produce IL-10, and the loss of these cells exacerbates the autoimmunity in murine models. Here, we report that CD38-/- mice exhibited elevated titres of ANAS, anti-dsDNA autoantibodies from 12 months of age and were higher by 16 months of age and mice presented kidney damage. Interestingly, there is a reduction in the survival of CD38-/- mice compared to the WT. Furthermore, CD38 is highly expressed by CD1dhigh CD5+ regulatory B cells, and the agonistic anti-CD38 stimulus plus LPS was able to increase the percentage of this cell subset and its ability to induce IL-10 production. Together, these results suggest that CD38 could play a role in the control of autoimmune diseases through their expression on regulatory B cells.
Assuntos
ADP-Ribosil Ciclase 1/deficiência , Anticorpos Antinucleares/imunologia , Doenças Autoimunes/genética , Linfócitos B Reguladores/imunologia , Interleucina-10/biossíntese , Glicoproteínas de Membrana/deficiência , ADP-Ribosil Ciclase 1/genética , ADP-Ribosil Ciclase 1/metabolismo , Animais , Doenças Autoimunes/imunologia , Autoimunidade/genética , Autoimunidade/imunologia , Células Cultivadas , Interleucina-10/imunologia , Nefropatias/imunologia , Lipopolissacarídeos/imunologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T/imunologiaRESUMO
The aim of this study was to determine the frequency of anti-prolactin autoantibodies and the relationship among anti-prolactin autoantibodies, serum prolactin (PRL) levels and lupus activity in paediatric patients with systemic lupus erythematosus (SLE) using a transversal study. One-hundred and three consecutive paediatric SLE patients were tested for serum anti-PRL autoantibodies and PRL levels. Clinical disease activity was scored using the SLEDAI index. Anti-PRL autoantibodies were measured by means of gel filtration. The frequency of anti-PRL autoantibodies was 6.7% (7/103), on the basis of the amount of immunoreactive PRL eluted in molecular weight fraction corresponding to IgG (150 kDa). No anti-PRL autoantibodies were found in normoprolactinaemic patients. By contrast, 21.8% (7/32) hyperprolactinaemic patients (hPRL) had anti-PRL autoantibodies. There was a correlation between anti-PRL autoantibody and serum levels of PRL (r(s) = 0.98, P = 0.0001). Lupus activity was present in 64/103 (62.1%) patients, without a significant difference in the frequency of anti-PRL autoantibodies when compared to inactive lupus (7.8 vs 5.1%, P > 0.05). Higher levels of serum PRL were associated with lupus activity regardless of other variables (39.6% vs 17.9%, P = 0.05). Patients with anti-PRL autoantibodies had higher levels of serum PRL than those without anti-PRL autoantibody (41.85 vs 17.77 ng/ml, P = 0.01) and significantly different frequency of hPRL (100 vs 26%, r = 0.4531, P < 0.001). We have identified a subset of paediatric SLE patients with hPRL and anti-PRL autoantibodies. Anti-PRL autoantibodies were associated with hPRL state and antibody titres correlated positively with serum PRL levels. These data suggest that anti-PRL autoantibodies could be responsible for hPRL in a subset of SLE patients. An increase in serum PRL levels proved to be related to lupus activity, but there was no statistical relationship between anti-PRL autoantibodies and lupus activity.
