| Objective:Sjogren’s syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into the salivary and lacrimal glands with concomitant destruction of the glandular tissue and autoantibody production. There are two types of Sjogren’s syndrome, primary or secondary form. Primary Sjogren’s syndrome presents alone, in the absence of other autoimmune or connective tissue disorders and impacts the salivary and lacrimal glands. The hallmark symptom of Sjogren’s syndrome is a generalized dryness, typically including xerostomia and keratoconjunctivitis sicca, part of what are known as sicca symptoms. Sjogren’s syndrome may affect other organs of the body, including the kidneys, lungs, liver, pancreas, peripheral nervous system (distal axonal sensorimotor neuropathy) and brain. There is neither a known cure for Sjogren’s syndrome nor a specific treatment to permanently restore gland secretion. Instead, treatment is generally symptomatic and supportive. For individuals with systemic manifestations and severe complications, such as pulmonary disease, vasculitis, and pancytopenia, corticosteroids, immunosuppressive drugs (cytotoxic agents), or both may be prescribed, and sometimes IVIG (intravenous immunoglobulin).Follicular helper T (TFH) cells are a recently identified CD4+T-cell subset, named for their location in GCs. TFHS are characterized by their signature transcription factor (Bcl-6), surface molecules (CXCR5, CD40L, ICOS, PD-1, etc), and cytokines (interleukin [IL]-21, IL-4, IL-10, etc). Through these signals, TFHS help B lymphocytes form GCs and promote the proliferation of B cells, then drive B cells to differentiate into memory B cells and plasma cells which produce antibodies. In recent years, the researches that the serum IL-21levels of SS patients were reported in the literature abroad occasionally, however, they had not elaborated the role for TFHS, which were known as the major source of IL-21, playing in the pathogenic mechanisms of SS. The preliminary study shows that there were numerous CXCR5+IL-21+T cells infiltrated in the labial salivary glands of patients with pSS, this found suggested that TFH was related to the pathogenesis of pSS. But how about the serum IL-21levels in circulation? Then, in our experiment, the IL-21concentrations in the serum from the healthy controls and pSS patients were measured and compared, the possible correlations between serum IL-21levels and clinical data (laboratory parameter and the types of systemic damage) of pSS patients were investigated, that aim to explore whether TFHS are involved in the pathogenesis of pSS. Thus, this finding may provide a clinical objective basis for suggesting that therapy directed at IL-21may be useful in pSS and other autoimmune disease.Materials:The experimental subjects were divided into two sections.①Obtaining40serum samples of resident pSS patients in the rheumatology ward of the Second Hospital of Hebei Medical University, during January2013to December2013, as the disease group. According to the different organs involved, the disease group was divided into6subgroups:5cases of secondary pulmonary interstitial disease,3cases of renal tubular acidosis,11cases of immune hemocytopenia,2cases of autoimmune liver disease,2cases of peripheral neuropathy,17cases of patients had no complications; The inclusion criteria included:the newly diagnosed patients were complied with the classification criteria for Sjogren’s syndrome in2002, ruled out other autoimmune and rheumatic diseases, had not received corticosteroids and immunosuppressive therapy before blood collection, without previous history of organ transplantation, viral hepatitis or HIV infection.②Obtaining30serum samples of healthy volunteers in the medical examination center of the Second Hospital of Hebei Medical University as the normal control group. The inclusion criteria included:people had normal laboratory indicators of blood routine, liver function, renal function, ESR, CRP and immunoglobulin (IgG, IgA, IgM), age and gender distribution matched the patients in experimental group, there was neither severe bacterial or viral infection history in the last two weeks, nor vaccination history in the last four weeks before blood sampling, without previous history of autoimmune disease, transplantation, viral hepatitis or HIV infection.Methods:The serum specimens of patients with pSS were gathered from fasting blood and preserved by-80℃for long-term, those of healthy controls were collected within a week before the experiment and preserved by-20℃instead. The serum IL-21levels of all specimens were measured by enzyme-linked immunosorbent assay (ELISA). In the experimental group, the erythrocyte sedimentation rates were determined by Westergren’s method, the Serum Immunoglobulin levels (IgG, IgA, IgM) were measured by immunoturbidime-tric assay, the anti-SSA/Ro and anti-SSB/La indexes were measured by counter immune electrophoresis and double immunodiffusion assay.Statistical analyses were performed by SPSS17.0(SPSS Company, Chicago, Illinois, USA). The data were expressed as the mean value±standard deviation (x±s). Differences in the mean IL-21levels between the two groups were analyzed by using the Student t-test. Differences in the mean IL-21levels of various subgroups in the pSS group were evaluated by using one-factor ANOVA analysis when the data were subject to normal distribution; if not, the overall comparison in each group was analyzed by using the Kruskal-Wallis H test. The linear correlation analysis was used to assess the correlation between the serum levels of IL-21and other laboratory data, then calculated the values of r as the Pearson correlation coefficient. Values of P <0.05were considered significant.Results:1Experimental group and control group comparison of clinical data:There was not statistically difference between age and gender distribution of the experimental group and healthy control group.2Experimental group and control group comparison of serum IL-21 levels:Compared with the serum IL-21levels of healthy controls, those were increased evidently in patients with pSS,(t=-11.347, P<0.01), that was considered statistically significant.3Comparisons of serum IL-21levels among different organs-involved subgroups with each others:Compared with the serum IL-21levels of pSS patients without systemic damagement, those were increased evidently in ones with various organs involvement, results were considered statistically significant.4Comparisons of serum IL-21levels in healthy controls with those among different organs-involved subgroups separately:Compared with the serum IL-21levels of healthy controls separately, those were increased evidently in pSS patients with various systemic damagement, results were considered statistically significant.5The serum IL-21levels of anti-SSA/Ro or anti-SSB/La ones in pSS group were compared with that of the antibodies negative ones and healthy controls:Compared with the serum IL-21levels of healthy controls and anti-SSA-/SSB-patients, those were increased evidently in patients with positive antibodies index,(t=-13.614,P<0.01and t=4.82,P<0.01), that was considered statistically significant.6Analysis the correlation between the serum IL-21levels and other laboratory data (ESR, IgG, IgA and IgM index) in pSS group:The linear correlation analysis illustrated:the serum IL-21levels of pSS patients correlated significantly with blood sedimentation and the serum IgG levels,(r=0.747,P<0.01and r=0.871,P<0.01), but there was no correlation with serum IgA and IgM levels.Conclusions:1Compared with the serum IL-21levels of healthy controls, those were increased evidently in patients with pSS, which suggested that cytokine IL-21was related to the pathogenesis of pSS; 2Compared with the serum IL-21levels of patients without organs involved, those were elevated evidently in patients with various secondary complications, which suggested that the overexpressed cytokine IL-21in the circulation was related to the mechanism of sytemic damage and amplify the histologic damagement in pSS.3The evident increase of serum IL-21levels in pSS patients had positive correlation with their anti-Ro/SSA or anti-La/SSB antibody index, which suggested that cytokine IL-21may enhance the secretion of autoantibodies.4The evident increase of serum IL-21levels in pSS patients had positive correlation with the levels of their ESR and IgG, which suggested that cytokine IL-21may promote the proliferation and differentiation of B cells, aggravate the condition of pSS, then play a critical role in the pathogenesis of pSS. |
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