Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10(-4)), oral ulcers (P = 6.9×10(-4)) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested

Liver involvement in primary sjögren's syndrome

Three hundred patients with primary Sjögren's syndrome (pSS) were investigated for liver involvement using clinical, biochemical, immunological and histological data.Seven percent of patients showed evidence of liver disease either subclinical (2%) or asymptomatic (5%) with elevated liver enzymes In 6.6 % of patients antimitochondrial antibodies (AMA) were detected by immunofluorescence and 27% of pSS patients showed antibodies to pyruvate dehydrogenase (a-PDH) using ELISA. AMA-positive patients were further investigated with transcutaneous liver biopsy. Ninety-two per cent of patients with AMA showed liver involvement with features of chronic cholangitis similar to stage I primary biliary cirrhosis It is concluded that liver involvement in pSS patients is rare and subclinical with histological features predominantly of stage I primary biliary cirrhosis AMA is the most sensitive indicator of underlying liver pathology in pSS patients. © 1994 British Society for Rheumatology

Increased prevalence of antibodies to thyroid peroxidase in dry eyes and mouth syndrome or sicca asthenia polyalgia syndrome

Objective. A subset of patients presenting with sicca features suggestive of primary Sjögren's syndrome (pSS) do not fulfill diagnostic or histopathological criteria. This presentation was previously designated as dry eyes and mouth syndrome (DEMS) or sicca asthenia polyalgia syndrome (SAPS). We sought to define the underlying clinical, laboratory, and histological features of these patients. Methods. The study population consisted of 27 consecutive patients with DEMS/SAPS; 54 patients with pSS served as controls. Medical charts were retrospectively evaluated for clinical and serological data and frozen sera were tested for the presence of antibodies against HIV, hepatitis C virus, and thyroid antigens. Immunohistochemical analysis of paraffin embedded tissues was also performed. Results. Sicca symptoms and nonspecific musculoskeletal pain were the commonest clinical features of patients with DEMS/SAPS; positive titers of antibodies against thyroid peroxidase was the main underlying abnormality found in 16 out of 27 (59.2%) of patients with DEMS/SAPS compared to 11 out of 54 (20.4%) of pSS controls (p = 0.0009). Histological analysis of the minor salivary gland (MSG) biopsies of patients with DEMS/SAPS disclosed a mild inflammatory infiltration of the interstitial tissue with a predominantly perivascular distribution. Conclusion. Patients with DEMS/SAPS present with sicca features and nonspecific musculoskeletal complaints, have high prevalence of antithyroid antibodies, and their MSG biopsies demonstrate a mild interstitial lymphocytic infiltration with a predominantly perivascular distribution. In the setting of clinical practice, we propose that in the presence of DEMS/SAPS testing for antithyroid antibody should be performed. The Journal of Rheumatology Copyright © 2009. All rights reserved

Cytokine mrna expression in the labial salivary gland tissues from patients with primary sjögren's syndrome

The pattern of cytokine mRNA expression in frozen minor salivary gland tissues from patients with primary Sjögren's syndrome (pSS) (n = 12) and controls (n = 8) using an in situ hybridization technique and oligonucleotide probes of interleukin-1β (IL-1β) tumour necrosis factorα and β (TNF-α and TNF-β), interleukin-6 (IL-6), interleukin-2 (IL-2) and its receptor (IL-2R), interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-γ (IFN-γ) and transforming growth factor-β(TGF-β) was examined. In addition to in situ hybridization, immunohistochemistry was used to identify the subset of cells expressing IL-2 and IL-4 mRNA. Mononuclear cells involved in the minor salivary gland lesions of pSS patients were found to express mRNA for pro-inflammatory cytokines such as TNF-α and IL-lβ, and cytokinesinvolved in the regulation of B- and T-cell function (IL-2 and IL-6). In contrast, only three biopsies from patients with pSS express mRNA of inhibitory cytokines such as IFN-γ and TGF-β. Furthermore mRNA for IL-6 and IL-1βwas also detected in the glandular epithelial cells suggesting that these cells may play a role in the pathogenesis of autoimmune lesion in Sjögren's syndrome. IL-10 mRNA was not detected while IL-4 mRNA was primarily detected in naive T-lymphocytes of patients with a mild and early lesion. These results suggest that local production of cytokines by both mononuclear and epithelial cells may be involved in the immune-mediated destruction of exocrine glands in patients with pSS. © 1995 British Society for Rheumatology

Salivary gland epithelial cells: A new source of the immunoregulatory hormone adiponectin

Objective. Adiponectin is an adipocytokine that displays insulin-sensitizing and immunoregulatory properties. Adipocyte development in association with fibrosis is frequently detected in primary Sjögren's syndrome lesions, connoting a healing process. The aim of this study was to examine the expression of adiponectin in minor salivary gland biopsy specimens obtained from patients with primary SS and controls. Methods. The expression of adiponectin in minor salivary gland biopsy specimens and in long-term-cultured non-neoplastic salivary gland epithelial cell (SGEC) lines obtained from patients with primary SS and control subjects was examined, using immunohistochemistry and immunoblotting, respectively. The expression of adiponectin, adiponectin receptor 1 (AdipoR1), and AdipoR2 messenger RNA (mRNA) by SGECs was investigated by reverse transcription-polymerase chain reaction. Results. Immunohistochemical analysis for adiponectin revealed positive staining of adipocytes from primary SS lesions as well as ductal epithelial cells from both patients with primary SS and controls. All of the SGEC lines tested were shown to express adiponectin, AdipoR1, and AdipoR2 mRNA, whereas adiponectin protein expression was detected by immunoblotting in SGECs from patients with primary SS but not in those from controls. The analysis of concentrated culture supernatants also revealed increased adiponectin expression by SGECs from patients with SS compared with controls. Conclusion. Our findings provide novel evidence that adiponectin is produced by SGECs. The high constitutive expression of adiponectin by SGECs from patients with primary SS is likely attributable to aberrant activation of these cells. Although the significance of adiponectin expression remains unknown, it is possible that adiponectin functions in an autocrine manner, as suggested by concurrent expression of the relevant receptors. © 2006, American College of Rheumatology

Liver involvement in Sjögren’s syndrome

Liver involvement in Sj\uf6gren\u2019s syndrome (SS) is commonly subclinical and almost never appears as the first manifestation of the disease. The prevalence of liver involvement in SS varies among series and depends on the diagnostic criteria used. Studies conducted in the 1960s, based on clinical (i.e., liver enlargement) and serological (i.e., elevated alkaline phosphatase) findings estimated the SS liver involvement as high as 20% [1]. A somewhat lower prevalence of liver disease has been reported in more recent studies, with estimates ranging from 2% to 20% of SS patients [2\u20136]

Mixed monoclonal cryoglobulinemia and monoclonal rheumatoid factor cross-reactive idiotypes as predictive factors for the development of lymphoma in primary sjögren's syndrome

Objective. To prospectively investigate whether mixed monoclonal cryoglobulinemia (MMC) and monoclonal rheumatoid factor (mRF)-associated cross-reactive idiotypes (CRI) serve as predictive factors for the development of lymphoma in patients with primary Sjögren's syndrome (SS). Methods. One hundred three consecutive patients with primary SS were evaluated from 1986 to 1991. In all patients, the amount of cryoglobulin was measured by ultraviolet absorption at 280 nm and 260 nm. The type of cryoglobulinemia was identified by agarose gel electrophoresis, combined with immunofixation. Sera from all patients were evaluated by enzyme-linked immunosorbent assay, using the corresponding monoclonal or polyclonal antibodies, for the presence of immunoglobulins bearing the idiotypes 17109 (VκIIIb associated), G-6 (VH1 associated), and 3rd SS (a rabbit polyclonal antibody raised against the Fab fragment of an IgMκ mRF from a patient with primary SS). Data analysis was performed by logistic regression. Results. Eighteen of the patients with primary SS (17.4%) had MMC during the first evaluation. There was a statistically significant correlation between the presence of MMC and a higher prevalence of autoantibodies to Ro/SS-A and La/SS-B, as well as extraglandular manifestations. During a 5-year period, 7 patients developed lymphoma. Six of the 7 (86%) had MMC before the appearance of lymphoma, compared with 12 of 96 (12.4%) of the remainder (r = 0.421, P < 0.0009). Patients who developed lymphoma had higher amounts of cryoglobulin than those who did not (mean ± SD 53.4 ± 44.7 mg/dl versus 26.8 ± 20.6 mg/dl). CRIs 17109 and G-6 were also correlated with lymphoma development (r = 0.321, P < 0.006 and r = 0.22, P < 0.03, respectively). For both CRIs, this correlation was dependent on the presence of MMC, since a stepwise multiple comparison analysis revealed that their individual significance was abolished when their correlation with lymphoma in association with MMC was assessed. Conclusion. The determination of MMC can be used as a laboratory predictive factor for lymphoma development in primary SS. CRIs 17109 and G-6 may also be used to predict lymphoma development, especially when the monoclonal component is absent