The numbers of Foxp3 + Treg cells are positively correlated with higher grade of infiltration at the salivary glands in primary Sjogren's syndrome.

This study was designed to investigate whether Foxp3( +) regulatory T (Treg) cells play a role in the histopathologic changes of primary Sjögren's Syndrome (pSS) and to evaluate other factors possibly associated with Foxp3(+) Treg cells in pSS patients. The number of FoxP3-expressing T cells in peripheral blood (PB) of 39 patients with pSS, 40 patients with rheumatoid arthritis (RA), and 28 healthy controls was measured by flow-cytometer analysis. FoxP3-expressing CD4(+)CD25(+) Treg cells were analyzed in minor salivary gland (SG) tissues of 39 pSS patients. Histopathologic changes were examined by light microscopy according to Chisholm's classification. Immunohistochemistry and immunofluorescence were performed to assess the Foxp3(+) Treg in SG biopsy specim-ens. The numbers of CD4(+) T cells and FoxP3-expressing CD4(+) T cells in PB were similar in all groups. Expression of CD25 on CD4(+) T cells in PB of patients with pSS and RA was significantly higher than in healthy controls, especially for RA patients. Immunohistochemistry and immunofluorescence showed that FoxP3(+) Treg were enriched in the SGs of pSS patients, with a positive correlation between the increase in FoxP3(+) Treg in SG and the Chisholm score in pSS (p < 0.001, r = +0.605). The increase of FoxP3( +) Treg cells in the SGs of pSS patients, which is correlated with gland infiltration, suggests that natural regulatory T cells play an important role in the pathogenesis of pSS. Further studies are required to explore the mechanisms that mediate the relationship between Treg and the pathogenesis of pSS.

Cardiac autonomic profile in rheumatoid arthritis and systemic lupus erythematosus.

Neurological involvement is a well-documented issue in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, little is known about the involvement of the autonomic nervous system. This study was conducted to investigate autonomic nervous system dysfunction in patients with RA and SLE. Twenty-six RA patients, 38 SLE patients and 40 healthy controls were recruited from our in- and out-patient departments. Heart rate variability (HRV) parameters (the power of the high- [HF] and low-frequency [LF] band of haemodynamic time series, the ratio between low- and high-frequency components [LF/HF ratio], the power spectral density), baroreflex sensitivity (BRS) and beat-to-beat blood pressures were assessed by a novel non-invasive haemodynamic monitoring tool (Task Force Monitor [TFM], CNSystems Medizintechnik GmbH, Graz, Austria). Autonomic nervous system dysfunction was determined according to classical Ewing autonomic test battery. Furthermore, we implemented a secondary autonomic test score by modifying the Ewing test battery with additional criteria. Both the classical and modified Ewing test batteries have revealed that the frequencies of autonomic neuropathy were significantly higher in patient groups compared with controls (p < 0.001). Evaluation by TFM revealed that deterioration of sophisticated autonomic parameters (such as HRV and BRS) were more pronounced in the patient groups compared with controls. There was a significant association between BRS and Ewing test scores and abnormal BRS results were more frequent in patients with autonomic dysfunction according to Ewing test batteries. No relation was found between autonomic neuropathy and disease duration, disease activity and autoantibody positivity. Consequently, we believe that further large-scale studies investigating cardiovascular autonomic neuropathy in rheumatic diseases should be carried out to verify our findings and manifest clinical consequences beyond these results.

CTLA-4 gene polymorphism of exon 1(+49 A/G) in Turkish systemic lupus erythematosus patients.

Cytotoxic T lymphocyte-associated antigen-4 is a cell-surface molecule providing a negative signal for T cell activation. CTLA-4 gene polymorphisms are known to be related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). However, the effects of this polymorphism on clinical features of SLE have not been defined. We analysed the CTLA-4 gene +49 A/G polymorphisms in patients with SLE by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and investigated the effect of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated Turkish SLE patients, all fulfilling the American College of Rheumatology criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA-4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015). There was a statistically significant difference in the AA genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27-5.56, P = 0.014] distribution among patients and controls. There was also an increase in A allele frequency in SLE and controls, but the difference was not statistically significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99-3.28). Interestingly, mean age and mean age of onset disease was higher in AA homozygote SLE patients compared to non-AA (39.2 +/- 11.5 vs. 31.6 +/- 10.6, P = 0.044; 32.38 vs. 24.31, P = 0.046, respectively). There was no association between genotype and the other clinical features of SLE. Our results suggested that CTLA-4 +49 AA genotype might be a risk factor for the development of SLE in Turkish population and G allele might be involved in early development of SLE. No association with clinical features was found for polymorphism of the promoter region in CTLA-4 +49.

Development of Crohn's disease following anti-tumour necrosis factor therapy (etanercept).

Inhibition of tumour necrosis factor (TNF)-alpha is effective in the treatment of rheumatoid arthritis and other inflammatory rheumatic diseases. Anti-TNF antibodies such as infliximab, etanercept and adalimumab are commonly used. There are structural and functional differences among these agents. We describe development of Crohn's disease in a patient with ankylosing spondylitis receiving anti-TNF therapy. This case suggests that the appearance of gastrointestinal symptoms in patients on anti-TNF therapy must be evaluated to find out whether this is a new onset or an exacerbation of underlying inflammatory bowel disease.