Salivary gland epithelial cell in Sjögren's syndrome: Metabolic shift and altered mitochondrial morphology toward an innate immune cell function.

Salivary gland epithelial cells (SGEC) are the main targets of the autoimmune reactivity in Sjögren's syndrome (SS). This study aimed to investigate the core proteomic differences between SS and Control- (Ct) -derived SGEC. Proteome analysis of cultured SGEC from five SS patients and four Ct was performed in a label-free quantitation format (LFQ). Electron microscopy was applied for analysis of the mitochondrial ultrastructure of SGEC in minor salivary gland sections from six SS patients and four Ct. Four hundred seventy-four proteins were identified differentially abundant in SS- compared to Ct-SGEC. After proteomic analysis, two distinct protein expression patterns were revealed. Gene ontology (GO) pathway analysis of each protein block revealed that the cluster with highly abundant proteins in SS-SGEC showed enrichment in pathways associated with membrane trafficking, exosome-mediated transport and exocytosis as well as innate immunity related mainly to neutrophil degranulation. In contrast, the low abundance protein cluster in SS-SGEC was enriched for proteins regulating the translational process of proteins related to metabolic pathways associated to mitochondria. Electron microscopy showed decreased total number of mitochondria in SS-SGEC, which appeared elongated and swollen with less and abnormal cristae compared to Ct-SGEC mitochondria. This study defines, for the first time, the core proteomic differences of SGEC between SS and Ct, substantiates the metamorphosis of SGEC into an innate immune cell and reveals that these cells are translationally shifted towards metabolism rewiring. These metabolic alterations are related mainly to mitochondria and are mirrored in situ with heavy morphological changes.

Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells.

The aim of this study was to examine the levels of endoplasmic reticulum (ER) stress in minor salivary glands, to investigate the interplay between ER stress-induced autophagy and apoptosis in human salivary gland (HSG) cells and to test the effect of ER stress-induced apoptosis on the cellular redistribution of the two major Sjögren's syndrome (SS) autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/Sjögren's syndrome-related antigen B (SSB). Minor salivary gland biopsies from SS patients and sicca controls were examined by immunohistochemistry for the expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell viability, autophagy and apoptosis were assessed. Immunoblot was applied to detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X-box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal epithelial cells in salivary glands of patients and sicca controls. TG treatment induced autophagy, as indicated by enhanced protein expression of LC3II. The protein levels of UPR marker XBP-1 were increased after TG treatment, while GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the cytoplasm in resting cells, while they were redistributed to cell membrane and blebs in the apoptotic cells. In conclusion, ER stress is activated in minor salivary gland epithelial cells from SS patients and controls. ER stress-induced apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization of Ro/SSA and La/SSB autoantigens.

Smokers and non smokers with rheumatoid arthritis have similar clinical status: data from the multinational QUEST-RA database.

OBJECTIVES: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. RESULTS: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). CONCLUSIONS: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).

Erythrocyte fatty acid composition and insulin sensitivity in daughters of Type 2 diabetic patients and women with no family history of diabetes.

BACKGROUND: There is evidence that the impact of environmental factors on insulin sensitivity is modified by the presence of family history of diabetes. AIM: To compare the association between the erythrocyte phospholipid fatty acid composition (a biomarker of dietary fatty acids) and insulin sensitivity in daughters of Type 2 diabetic patients with the corresponding association in women without family history of diabetes. MATERIAL/SUBJECTS AND METHODS: Eighteen offspring of Type 2 diabetic patients [age 30+/-6.5 yr; body mass index (BMI) 22.2+/-2.5 kg/m2; body fat 31.8+/-5.1%] and 18 matched women (age 30.1+/-6.8 yr; BMI 22.2+/-1.8 kg/m2; body fat 32.2+/-6.0%) participated in the study. RESULTS: Insulin Sensitivity Index (ISI)-Matsuda tended to be lower (p=0.06) in the Offspring than the control group. Weight proportions of erythrocyte phospholipid saturated (SFA), polyunsaturated (PUFA), and monounsaturated fatty acids (MUFA) were similar between the two groups. In the offspring, erythrocyte total SFA were negatively correlated with ISI-Matsuda [r=-0.47, p<0.05), ISI(gly)-Belfiore (r=-0.52, p<0.05) and ISI(ffa)-Belfiore (r=-0.53, p<0.05)], whereas total PUFA were positively correlated with insulin sensitivity [ISI-Matsuda, r=0.46, p<0.05; ISI(gly)-Belfiore, r=0.53, p<0.05; ISI(ffa)-Belfiore, r=0.54, p<0.05]. No significant correlations were observed in the control group. CONCLUSIONS: The associations between erythrocyte fatty acid composition and insulin sensitivity are distinct between daughters of Type 2 diabetic patients and women without family history of diabetes.

Cryoglobulinemic vasculitis in primary Sjögren's Syndrome: Clinical presentation, association with lymphoma and comparison with Hepatitis C-related disease.

OBJECTIVE: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. METHODS: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. RESULTS: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7-20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7-14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. CONCLUSION: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS.

Clinically significant and biopsy-documented renal involvement in primary Sjögren syndrome.

Clinically significant renal involvement in patients with primary Sjögren syndrome (pSS) has been described previously only in isolated case reports. The prevalence and significance of the 2 described syndromes, interstitial nephritis (IN) and glomerulonephritis (GMN), are not well known. In a cohort of 471 patients with pSS who were followed for a mean of 10 years, 20 patients (4.2%) developed overt renal disease. Eighteen patients underwent a percutaneous renal biopsy; 2 patients declined. Ten patients had IN, 8 patients had GMN, and 2 patients presented with both entities. Glomerular histology disclosed changes compatible with membranoproliferative GMN in 5 patients and mesangial proliferative GMN in 4 patients. Patients with IN had a younger disease onset compared with patients with GMN (mean, 36.8 compared with 46.0 yr, p 5 0.063). Patients with GMN had longer disease duration compared with patients with IN (mean, 2.2 compared with 8.0 yr, p 5 0.001). The majority of patients with GMN (80%) had mixed monoclonal cryoglobulinemia IgMk (type II) and lower complement C4 levels. Two patients (both with GMN) developed chronic renal failure requiring hemodialysis. Overall, clinically significant renal involvement is infrequent in pSS. IN occurs early in the disease process, while GMN is a late sequela and may have a less favorable prognosis.

Molecular analysis of HLA class II genes in primary Sjögren's syndrome. A study of Israeli Jewish and Greek non-Jewish patients.

In an attempt to define the role of HLA class II genes in predisposition to primary Sjögren's syndrome, patients of two different ethnic groups (Israeli Jews and Greeks of non-Jewish origin) suffering from this disorder were studied. Oligonucleotide genotyping revealed the majority in both groups to carry either DRB1*1101 or DRB1*1104, alleles that are in linkage disequilibrium with DQB1*0301 and DQA1*0501. The high frequency of the two alleles in these SS patients is in contrast with the accepted association of primary SS with HLA-DR3 in Italian and American individuals. Molecular analysis of DQB1 and DQA1 alleles found in American Caucasian and American black SS (or SLE) patients demonstrated high frequencies of DQB1*0201 and DQA1*0501. The fact that the majority of SS patients, across racial and ethnic boundaries, carry a common allele, DQA1*0501, implies its involvement in the predisposition to primary SS. Based on sequence analysis and the computer imaging of the HLA class II molecule structure, a hypothetical model for the role of the DQ molecule in promoting primary SS is proposed.

Clinical evolution, and morbidity and mortality of primary Sjögren's syndrome.

OBJECTIVES: To study the clinical and laboratory profile evolution, as well as morbidity and mortality impact, of primary Sjögren's syndrome (pSS), in a large cohort of patients followed-up longitudinally. METHODS: We studied the evolution of the clinical picture and laboratory profile of pSS, the incidence and predictors for systemic sequelae, and the impact of pSS on overall survival in a prospective cohort study of 261 patients with pSS. Analyses included calculation of incidence rates, Cox proportional hazards predictive models, and estimation of standardized mortality ratios (SMRs) compared with the general Greek population, adjusting for age and sex. RESULTS: Glandular manifestations of the syndrome were typically present at the time of diagnosis. Systemic manifestations such as arthritis, Raynaud's phenomenon, purpura, interstitial nephritis, and liver involvement, as well as the serological profile, also did not change substantially during subsequent follow-up. Incidence rates for peripheral neuropathy, glomerulonephritis, and lymphoproliferative disorders were 3.3, 6.6, and 12.2 per 1,000 person-years, respectively. Glomerulonephritis and lymphoma tended to co-exist in the same patients (relative risk, 34.0; P < .0001). The development of lymphoproliferative disorders was associated with low levels of C4 complement (relative risk, 7.5; P = .0016), the presence of mixed monoclonal cryoglobulins (relative risk, 7.9; P = .0012), and purpura (relative risk, 3.9; P = .037). Low levels of C4 was the strongest predictor for mortality after adjusting for age (relative risk, 6.5; P =.0041). Patients with pSS had an SMR of 2.07 (95% CI, 1.03 to 3.71). However, when patients with adverse predictors were excluded, the mortality rate was identical to that of the general population (SMR 1.02). CONCLUSIONS: The initial presentation of pSS determines subsequent outcome. Purpura, decreased C4 complement levels, and mixed monoclonal cryoglobulinemia are adverse prognostic factors. The overall mortality of patients with pSS compared with the general population is increased only in patients with adverse predictors.

Neuroendocrine manifestations in Sjögren's syndrome.

Molecular biology has had a major impact on our concepts of the immune system and its relation to neuroendocrine axes, in particular, the adrenal, gonadal, and thyroid axes. It is now well established that not only are the biosynthetic and catabolic pathways of glucocorticoids and sex hormones (estrogen, progesterone, and testosterone) closely related but that the receptors for these hormones are part of a supergene family of receptors which include (in addition to these hormone receptors) the mineralocorticoid receptor, thyroid hormone receptor, retinoic acid receptors, and vitamin D receptors. This suggests a complex network of steroid hormones and receptors for the control and integration of a multitude of physiologic functions at a systemic level. The immune system seems to be tightly integrated into this homeostatic neuroendocrine regulatory network. The neurophysiologic and biochemical events that promote successful adaptation during stressful situations are now identified for illnesses that seem to occur as a result of or are associated with dysregulation of the stress response. One difficulty in interpreting the mechanisms of HPA axis dysfunction in autoimmune-inflammatory syndromes arises from the plasticity of the hormonal systems involved. Levels of hormones produced and receptors reset rapidly with changes in the hormonal milieu (deficiency or excess) and have likely changed during the course of the chronic immune disorder. This, in turn, is further confounded by the pleomorphic natural history of most autoimmune-inflammatory diseases such as SS. The levels of sex hormones and their receptors are tightly linked to HPA axis function. It may be that significant changes in the estrogen-to-androgen ratio or the ratio of their receptors alter the activity of steroid-sensitive cells such as the individual immune cells or epithelial cells, thus providing a means for endocrine regulation of the immune response in SS. Studies in the closely related disorder RA support this hypothesis. Taken together, adrenal and gonadal steroid hormone deficiency plus elevated PRL levels probably greatly facilitate cellular immunity in SS patients. This hypothesis in SS is supported by a growing body of data indicating that RA develops as a consequence of a deficiency in adrenal and gonadal steroid hormone production. It is noteworthy that the findings in female SS patients indicated a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid. At present, it is not clear if any one system plays a primary role in the expression of the disease. Rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones, making the specific effects of individual hormones difficult to discern.

Autoimmune epitheliitis: Sjögren's syndrome.

Sjögren's syndrome (SS), an autoimmune exocrinopathy, is a common, chronic disease of females. Clinical studies of kidney involvement in SS patients have shown that the predominant lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one fourth of SS patients suffer from subclinical interstitial lung disease. Re-evaluation, however, of the pulmonary disease using functional, radiologic and histopathologic studies showed that the lesion starts peribronchially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the systemic manifestations of SS are probably due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the proto-oncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients by in situ hybridization revealed that the proinflammatory cytokines IL-1 and IL-6 are also produced by the epithelial cells. Finally, proviral DNA has been shown to be incorporated in the DNA of epithelial cells. On the basis of these clinical and laboratory observations, we would like to suggest that the target tissue involved in the autoimmune histopathologic lesions of SS is the epithelium, and therefore we propose the term "Autoimmune Epitheliitis" instead of "Sjögren's syndrome" for this disease.

Paravertebral leiomyosarcoma mimicking a chronic ongoing inflammatory process.

Leiomyosarcomas usually present with symptoms associated with the tumor site or as painless soft tissue masses. We report the case of a young woman with spiking fever and elevated acute reaction proteins for months, in the context of a paravertebral high grade leiomyosarcoma.

Methotrexate in primary Sjögren's syndrome.

OBJECTIVE: To determine the safety and efficacy of methotrexate (MTX) in the treatment of primary Sjögren's syndrome (SS). METHODS: An open, one-year pilot study of MTX (0.2 mg/kg body weight taken weekly) for the treatment of SS was performed. Seventeen patients with primary SS according to EEC criteria were enrolled in the study. Outcome was determined on the basis of clinical and laboratory parameters. RESULTS: Weekly administration of MTX resulted in improvement of the main subjective symptoms (dry mouth and eyes) as well as in the frequency of parotid gland enlargement, dry cough and purpura. However, no improvement in the objective parameters of dry eyes and dry mouth were observed. Persistent asymptomatic elevation of the hepatic transaminase levels led to a dosage reduction in 7 patients (41%). CONCLUSIONS: Weekly MTX may be an acceptable form of therapy for SS patients. Double-blind trials are needed to substantiate the efficacy of this therapeutic modality.

Evaluation of unstimulated whole saliva flow rate and stimulated parotid flow as confirmatory tests for xerostomia.

Unstimulated whole saliva collection (U.W.S.C.) and stimulated parotid flow rate (S.P.F.R.) are routine tests for evaluation of xerostomia. Different groups of investigators, however, use different normal values; some prefer one test (either one) more than the other. This prompted us to evaluate these tests in 81 well documented primary Sjögren's syndrome (prim. SS) patients and 188 age and sex matched normal volunteers. The U.W.S.C. as well as the S.P.F.R. were performed for 5 min. Lemon juice was used for stimulation and the saliva from the parotid gland was collected using modified Carlson-Crittenden cups. Normal individuals produced from between 0.20 and 6.81 ml/5 min (x +/- SD: 2.03 +/- 1.36 ml) of U.W.S. and from between 0.00 and 7.50 ml/5 min (x +/- SD: 1.00 +/- 1.10 ml) of S.P.F. No statistical differences were observed between the two salivary flow rates. Primary Sjögren's syndrome patients produced from 0.04 to 2.00 ml/5 min (x +/- SD: 0.47 +/- 0.50 ml) of U.W.S. and from 0.00 to 2.00 ml/5 min (x +/- SD: 0.37 +/- 0.56 ml) of S.P.F. Using the 95% confidence limit of the flow rates (U.W.S.: 1.25 ml/5 min and S.F.P.: 1.5 ml/5 min) observed in prim. SS patients, it was observed that 57% of the U.W.S. and 78% of the S.P.F values produced from normal individuals fall into that range. Based on these findings we conclude that these two tests are not useful for the evaluation of xerostomia.

Sjögren's syndrome in rheumatoid arthritis and progressive systemic sclerosis. A comparative study.

One hundred and eleven patients with rheumatoid arthritis (RA) and 44 with progressive systemic sclerosis (PSS) were prospectively evaluated for evidence of Sjögren's syndrome (Ss). The diagnosis was established when a patient with a lip biopsy focal lymphocytic infiltration score of greater than or equal to 2+ in Tarpley's scale had keratoconjunctivitis sicca (KCS) and/or xerostomia. Out of 44 RA and 10 PSS patients with positive lip biopsy, 34 and 9 had criteria for Ss respectively, suggesting a 31% prevalence of Ss in RA and a 20.5% in PSS. Six per cent of the RA patients spontaneously offered complaints of subjective xerophthalmia whereas 11.1% and 22.2% of those with PSS did so for subjective xerophthalmia and xerostomia respectively. However, specific questionnaire elicited subjective xerophthalmia in 38.2% and subjective xerostomia in 5.9% of the RA patients, whereas in 55.5% and 66.7% of the PSS ones respectively. Parotid gland enlargement was detected in 20.6% of the RA and in 44.4% of the PSS patients with Ss. Anti-Ro (SSA) antibodies were present in the sera of 23.5% and 33.3% of them respectively. Severe extraglandular manifestations were unusual in both groups. Our results suggest that, although both Ss in RA and that in PSS lack prominent exocrine gland symptomatology, certain differences between the two and similarities of the latter to primary Ss, would not justify the term 'secondary Ss' for the syndrome accompanying scleroderma, as it has been applied to that accompanying RA.

Nandrolone decanoate (deca-durabolin) in primary Sjögren's syndrome: a double blind pilot study.

The efficacy and side-effects of Deca-Durabolin (DD) were tested, in a double blind fashion, in twenty female primary Sjögren's syndrome (1 degree SS) patients. Ten randomly assigned patients received DD (100 mg IM bi-weekly) for six months, and ten others placebo, for the same period. Analysis of the results revealed that the DD-treated patients showed a moderate improvement of subjective xerostomia, a significant decrease of the erythrocyte sedimentation rate (ESR), and an overall improvement of their feeling of well-being, -judged by themselves and the investigator subjectively-, when compared with the placebo group. All the sicca objective parameters (results of Schirmer's I test, slit lamp eye examination after rose bengal staining, stimulated parotid flow rate measurements and labial minor salivary gland histopathology) were not significantly altered in either group. The clinical side-effects were the expected ones, i.e. hirsutism, hoarseness and an increase in libido, more pronounced in the DD-treated group. At the end of the study, one DD-treated patient, developed a diffuse well-differentiated B-lymphocytic lymphoma, which regressed spontaneously three months later.

Association of mast cells with fibrosis and fatty infiltration in the minor salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: To determine the distribution and density of mast cells in the minor salivary glands of patients with primary Sjögren's syndrome (pSS) and of normal controls. METHODS: Minor salivary gland biopsies were obtained from 19 patients with pSS, 9 with systemic lupus erythematosus, one each with rheumatoid arthritis, sarcoidosis, and Hodgkin's disease, and from 10 individuals who had subjective xerostomia with normal salivary gland biopsies. Biopsy specimens were evaluated for the degree of inflammation according to Tarpley's classification. Sections were analysed for staining with Toluidine blue and with the mast cell specific marker c-kit. The data obtained were correlated with the histological findings of fatty infiltration, fibrosis and lymphocytic infiltration. RESULTS: There was a significant correlation between the number of mast cells identified and the degrees of fibrosis and fatty infiltrates. There was no correlation between the intensity of lymphoid infiltration and the number of mast cells. c-kit staining showed a high correlation when compared to Toluidine blue staining. CONCLUSION: Mast cells in the minor salivary glands of patients with pSS are strongly associated with fibrosis and cell acid infiltration. However, there is no correlation with parameters of disease activity such as lymphoid infiltration.

Erythema nodosum: the underlying conditions.

Erythema nodosum (EN) is a cutaneous reaction consisting of inflammatory, tender nodular lesions and is associated with a wide variety of disease processes. The aim of our study was to investigate the frequency of different aetiologies of EN. One hundred and thirty-two EN patients were investigated in a prospective study during the period 1984-1990. The evaluation of all patients began with a medical and family history and completed with a thorough physical examination and detailed laboratory and immunological work-up. In addition, various diagnostic procedures were performed where and when indicated. One hundred and ten patients (83%) were women. Their mean age was 41.0+/-14.0 years, range 18-79 years. In 35% the cause of EN was not found. Sarcoidosis was revealed in 28% of the patients, infections in 17.3% and tuberculosis in 1.5%. Other aetiologic factors were Adamantiadis-Behçet's syndrome (3.8%), pregnancy (6%), oral contraceptives (3.8%) and other drugs (3.8%). The aetiology of EN was not found in 35% of the patients. Sarcoidosis and infections were frequent causes of EN, whereas autoimmune rheumatic diseases rarely cause EN.

[Sterile corneal ulcers in dry eye. Incidence and factors of occurrence]. / Les ulcères cornéens stériles de l'oeil sec. I. Fréquence et facteurs de leur apparition.

Sterile corneal ulceration is a serious complication in patients with keratoconjunctivitis sicca. The records of 134 patients, 19 males and 115 females, who presented with dry eyes in the Ophthalmologic Clinic were reviewed. Over a period of 6 years, 33 eyes of 23 (17%) patients developed a sterile corneal ulcer. The etiologies of dry eyes in these patients were: Primary Sjogren's syndrome: 10 cases, rheumatoid arthritis: 5 cases, ocular pemphigoid 6 cases, atopy: 1 case, local irradiation: 1 case. Patient's age and sex were not significantly associated with ulcer development (p greater than 0.05). The presence of a major underlying disease was the major contributing factor. Appropriate local treatment and patient compliance were also contributing factors. Blepharitis was found in 90% of patients.

[Evaluation of clinical symptoms and laboratory data as diagnostic criteria for Sjögren's syndrome]. / Otsenka klinicheskikh simptomov i laboratornykh priznakov v kachestve diagnosticheskikh kriteriev sindroma Segrena.

In this study the authors evaluated the sensitivity, specificity and misclassification error rate of the following parameters: subjective xerophthalmia (questionnaire), positive Schirmer's I test less than or equal to 5 mm/5 min, positive rose-bengal staining on slit lamp examination, subjective xerostomia (questionnaire), abnormal stimulated parotid flow rate less than or equal to 0.5 ml/5 min and recurrent parotid gland enlargement. Thirty-two patients with primary SS (pSS), 40 patients with some of the criteria for pSS, 20 patients with SS in association with RA (sSS), 45 patients with RA and some of SS criteria and 29 RA patients without any clinical or histological manifestations of SS participated in this study. The minor salivary gland histopathology (focal lymphocytic infiltrates greater than or equal to 2+ (T. M. Tarpley et al., 1972) was taken as prerequisite for the diagnosis of SS and the absence of any clinical or serological manifestations of other autoimmune disease for the diagnosis of pSS. Based on this analysis the authors suggested that definite pSS can be diagnosed in the absence of any other autoimmune disease, positive labial biopsy and the presence of subjective xerostomia or parotid gland enlargement or positive rose-bengal staining, and definite sSS if a patient has RA, positive labial biopsy and subjective xerophthalmia or positive rose-bengal staining.

[HLA antigens in patients with Sjögren's syndrome]. / HLA-antigeny u bol'nykh s sindromom Shegrena.

HLA-antigens were studied in 116 Greek patients: 22 with pSS, 14 with sSS and RA, 26 with classical RA and 420 healthy controls. A statistically significant increase in HLA-DR5 was observed mainly in pSS patients with anti-Ro (SSA). A significant increase in HLA-B8, HLA-DR3 and HLA-DR5 was observed in pSS patients with anti-La (SSB) antibodies as compared to the controls.