anti-SSB Antibodies Research Articles

Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry

Pulmonary arterial hypertension (PAH) is a rare complication of systemic lupus erythematosus (SLE). We identified all patients with SLE and PAH (SLE-PAH) who were enrolled in the French Pulmonary Hypertension Registry with a diagnosis confirmed by right heart catheterization (RHC). A control group of 101 patients with SLE without known PAH was selected from SLE expert centers participating in the Pulmonary Hypertension Registry. Survival was estimated by the Kaplan-Meier method. Hazard ratios associated with potential predictors of death were estimated using Cox proportional hazard models. Of the 69 patients with SLE-PAH identified in the French Pulmonary Hypertension Registry, 51 were included in the study. They did not differ from the control group regarding age, sex, or duration of SLE at the time of the analysis but had a higher frequency of anti-SSA and anti-SSB antibodies. The delay between SLE diagnosis and PAH diagnosis was 4.9 years (range, 2.8-12.9) years. The 3- and 5-year overall survival rates were 89.4%(95%CI, 76.2%-96.5%) and 83.9%(95%CI, 68.8%-92.1%), respectively. The survival rate was significantly better in patients with anti-U1-RNP antibodies (P= .04). Patients with SLE-PAH have an overall 5-year survival rate of 83.9%after the PAH diagnosis. Anti-SSA/SSB antibodies may be a risk factor for PAH, and the presence of anti-U1-RNP antibodies appears to be a protective factor regarding survival.

P264 Sjögren’s syndrome presenting with myelitis and without SICCA symptoms

Sjogren’s syndrome (SS) is a chronic inflammatory disorder of exocrine glands with autoimmune etiology. Sjogren’s syndrome affect the nervous system in approximately 20% of cases. The prevalence of peripheral and central neurological manifestations in Sjogren syndrome are about 15% and 5% respectively. Neurological symptoms may occur before the onset of SICCA symptoms (dry eyes and dry mouth). Anti-Ro/SSA and anti-La/SSB antibodies are present 50–70% of patients with Sjogren syndrome. Patients with SS that have neurological symptoms, only 21% have anti-SSA or anti-SSB antibodies. In this article, we report a patient with SS, presenting as myelitis without any SICCA symptoms and without any Anti-Ro/SSA and anti-La/SSB antibodies in the sera of patient. Most common peripheral nervous system (PNS) presentations are axonal polyneuropathies (distal axonal sensory and sensorimotor), sensory ganglionopathy, motor neuropathy, small fiber neuropathy, multiple mononeuritis, trigeminal and other cranial neuropathies, autonomic neuropathies, demyelinating polyradiculoneuropathy. The sensory neuropathies constitute the most frequent PNS complication. Central nervous system (CNS) manifestations of Sjogren’s syndrome may affect spinal cord, brain stem, optic nerves, cerebellum, and cerebral hemispheres. CNS involvement is much less common than peripheral nervous system involvement. Transverse myelitis is an inflammatory disorder of the spinal cord that presents acutely. The presence of sensorial axonal polyneuropathy and longitudinally extensive transverse myelitis that spans the servical and thoracic spinal cord led us thinking about SS. The positive Schirmer’ test and lip biopsy supported the diagnosis of SS. So, it is important to consider SS in differential diagnosis even if there is no SICCA syndrome or even if autoantibodies are negative.

Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus

BackgroundDilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. MethodsWe analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. ResultsAmong 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth–36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20–8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81–9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94–15.47]).Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth–4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months–22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63–4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. ConclusionNeonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB.

Expression and its promoter methylation of chemokine CXC ligand 14 in peripheral blood mononuclear cells from patients with lupus

To analyze the expression and its promoter methylation of chemokine CXC ligand 14 (CXCL14) in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). The RNAs of PBMCs from 28 SLE patients and 20 healthy controls were isolated and reversely transcribed into cDNAs. Using GAPDH as the internal reference, the levels of CXCL14 ex-pression were detected by real-time polymerase chain reaction (PCR). The correlation between CXCL14 expression and the clinic pathological fe atures of SLE were further analyzed. DNA methylation was analyzed by bisulfite sequencing PCR (BSP). Our data indicated that the level of CXCL14 in the PBMC of SLE patients was statistically lower than that in healthy controls (P < 0.05). Further analysis showed that CXCL14 expression was negatively correlated with anti-Sj gren syndrome B antibody(anti-SSB antibody, P < 0.01) and albuminuria(P < 0.05). However, CXCL14 expression was not significantly correlated with the indexes of SLE activity, renal damage, the level of anti-ds-DNA antibodies, complement C3 and C-reactive protein. In addition, we further demonstrated that the CXCL14 promoter hypermethylation expres-sion was significant higher than healthy controls. Down-regulated of CXCL14 expression in PBMC maybe involved in the occur-rence or development of SLE disease. The loss of CXCL14 expression was regulated by promoter hypermethylation.

Increased Interleukin-17F is Associated with Elevated Autoantibody Levels and More Clinically Relevant Than Interleukin-17A in Primary Sjögren's Syndrome.

Th17 related immune response is pathogenic in primary Sjögren's syndrome (pSS). However, the role of IL-17F, one potent inflammatory member of IL-17 family cytokines in pSS, has not been specifically defined. We recruited one hundred and nine pSS patients and forty-two healthy controls and their serum levels of IL-17A and IL-17F were determined by multiplex cytokine assays. White blood cell, red blood cell, neutrophil, lymphocyte, IgM, IgG, C3, C4, RF, ANA, anti-SSA antibody, and anti-SSB antibody were measured by standard laboratory techniques. EULAR Sjögren's syndrome disease activity index (ESSDAI) score was also evaluated accordingly. We found that IL-17F was significantly increased in pSS patients. Elevated levels of IL-17F were associated with increased IgG and IgM, higher titers of ANA and anti-SSA antibodies, and reduction of C3 and C4. Patients with higher disease activity also showed higher serum IL-17F levels. However, serum IL-17A was only increased in patients with longer disease duration and showed few correlation with clinical and laboratory features in pSS patients. In conclusion, IL-17F was correlated with increased autoantibody levels and disease activity in pSS and is more clinically relevant than IL-17A.

Clinical & immunological characteristics in systemic lupus erythematosus patients.

Background & objectives:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which affects females more than males. Gender affects the manifestations of SLE and men with lupus show more severe symptoms and worse prognosis. This study was aimed to compare clinical and immunological features in female and male lupus patients in Iran.Methods:Demographic, clinical and laboratory data from 78 women and 20 men with lupus were collected. Autoantibodies (against nRNP, Sm, SSA, SSB, Ro-52, CENP, Jo-1, Scl-70, nucleosome, anti-dsDNA, histone and Rib-p protein) were determined using immunoblotting technique.Results:Men with lupus had less anti-SSA (21.1 vs 48.1%) and anti-Ro52 (10.5 vs 44.3%) antibodies when compared to women and none of the male patients had anti-SSB antibodies. Kidney damage was more frequent in men (68.4% in men vs 36.7% in women). In men with kidney involvement, anti-dsDNA increased significantly (84.6 vs 20.0%) in comparison to males without nephritis. Anti-SSA (7.7 vs 50.0%) and anti-nRNP (0.0 vs 33.8%) on the other hand, decreased. Women with renal involvement had no anti-SSB antibodies.Interpretation & conclusions:In male patients, SLE appeared with more severe features, and kidney damage was more frequent in males. The frequency of some autoantibodies was different between females and males. In males with kidney damage anti-dsDNA increased significantly, while anti-SSA and anti-nRNP decreased. Anti-SSB was not detected in males and females with nephritis.

A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren's syndrome.

Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment. We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American-European Consensus Group criteria or enlarged American-European Consensus Group criteria, and with biopsy-proven renal involvement. A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of <60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m 2 at baseline, P < 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study. Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease.

Characteristics of primary Sjögren's syndrome patients with IgG4 positive plasma cells infiltration in the labial salivary glands.

The purpose of this study was to investigate the characteristics of primary Sjögren's syndrome (pSS) patients with IgG4 positive (IgG4+) plasma cell infiltration in labial salivary glands (LSGs). Paraffin sections of LSGs from 336 pSS patients were stained with IgG4 and IgG monoclonal antibodies. According to the infiltration of IgG4+ plasma cells, patients were divided and clinical and serological characteristics were analyzed and compared. Based on the infiltration of IgG4+ plasma cells in the LSGs, patients were divided into three subgroups, low IgG4, moderate IgG4, and high IgG4 groups. A negative association between the number of infiltrated IgG4+ plasma cells and the disease characteristics was observed. We found that the higher the IgG4+ expression in plasma cells, the lower the positive rates of serum anti-SSA antibodies, anti-SSB antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF). Besides, patients from the high IgG4 group had the highest frequency of interstitial lung disease (ILD, 30.6%) and tubulointerstitial nephritis (TIN, 13.9%), but the lowest frequency of leucopenia (13.9%), thrombocytopenia (11.1%), and abnormal thyroidal function (0%). PSS patients with different IgG4+ plasma cells infiltration in the LSGs had distinctive clinical and laboratory characteristics. It may help us to further understand the role of IgG4+ plasma cells in pSS.

Cystic lung disease in Sjögren's syndrome: An observational study

ObjectivesTo analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjögren's syndrome (SS). MethodsFrom June 2010 to February 2015, 90 consecutive SS patients [60.1±14.8years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin-walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records. ResultsTwenty-one (23.3%) patients had cysts on CT scan performed 40.5±54.5months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n=6, 28.6%) or associated with other lesions, including bronchiectasis (n=5, 23.8%), micronodules (n=5, 23.8%), ground-glass opacity (n=4, 19%) and/or air trapping (n=3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3±15.3 versus 58.5±14.4years, P=0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P=0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1±17.7months), no patient developed specific lung disease or lymphoproliferative disorders. ConclusionsCystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS.

Increased cancer incidence in SICCA syndrome patients positive for anti-centromere antibody

Objectives: The main purposes of this study were to determine the clinical significance of the presence or absence of the anti-centromere antibody in SICCA Syndrome and to diagnose the symptoms. Methods: We retrospectively investigated the prevalence of ACA in patients with SICCA syndrome between January 2006 and January 2014 in Kaohsiung Chang Gung Memorial Hospital. We compared ACA-positive patients with ACA-negative patients. Results: Clinical manifestations in ACA-positive patients are shown in table 2. Many of the clinical symptoms were primarily associated with the predominant disease, scleroderma, limited scleroderma, systemic lupus erythematosus or Sjogren's syndrome (SS). Myalgia was the most prevalent manifestation among those that were ACA-positive. There were fewer ACA-positive SICCA patients with anti-SSA or anti-SSB antibodies than ACA-negative SICCA patients (p ＜0.01, p = 0.011, respectively). Among 35 ACA-positive patients, SS was found in 21 patients (60.0 %), including 13 with primary SS and 8 with secondary SS. In the other 14 patients, 8 had cancer and 6 had other diseases. Among 36 ACA-negative patients, SS was found in 33 patients (91.6 %), including 29 with primary SS and 4 with secondary SS. In the other three patients, one had cancer and two had thyroid diseases. The incidence of cancer was significantly higher in the ACA-positive group than in the ACA-negative group [odds ratio = 10.37; 95 % confidence interval (CI), 1.22-88.02; p ＜ 0.05]. Conclusion: In our study, ACA-positive patients with SICCA syndrome had increased incidence of cancer (p ＜ 0.01; odds ratio = 10.37) and lower prevalence of anti-SSA/anti-SSB antibodies. With regard to cancer risk, anti-centromere positive SICCA syndrome patients should be carefully evaluated for early diagnosis of cancer.

Clinical and immunological consequences of total glucosides of paeony treatment in Sjögren's syndrome: A randomized controlled pilot trial

BackgroundThe total glucosides of paeony (TGP) can inhibit inflammation and alleviate symptoms in autoimmune diseases. This study investigated the clinical and immunological consequences of TGP treatment in patients with primary Sjögren's syndrome (SS). MethodsWe conducted a randomized, double-blinded, placebo-controlled clinical trial in 45 patients with primary SS. Patients were randomized at 2:1 ratio to either TGP group (n=29) or placebo group (n=16) and followed up for 24weeks. The primary outocme was the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI). The secondary outcomes were stimulated and unstimulated salivary flow rate, Schirmer's test and erythrocyte sedimentation rate (ESR), immuneglobulin (Ig), anti-nuclear antibody (ANA), anti-SSA, and anti-SSB. The proportions of B cells in peripheral blood and the levels of serum inerleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and B cell activating factor belonging to the TNF family (BAFF) were measured at baseline and at the end of follow up of 24weeks. ResultsThe average score of ESSPRI in both groups had no statistical significance at 24th week. The mean of ESSPRI in the dry-mouth part of questionnaire in patients who scored 3 to 6 points was significantly reduced in the TGP group changed from (4.81±0.60) at baseline to (4.20±1.46) (P=0.027) at week 24. Stimulated salivary flow rate increased at week 24 from (1.80±0.39) to (2.01±0.51) (P=0.031) and unstimulated salivary flow rate increased from (0.65±0.46) to (0.78±0.45) (P=0.011) in the TGP group, but the placebo group showed no significant difference. Erythrocyte sedimentation rate (ESR) was decreased significantly compared to the placebo group at 12- and 24-week from (40.9±18.0) to (29.4±12.2) (P=0.003) and (30.4±17.3) (P=0.024). The percentage of naive B cells decreased at week 24 in the TGP group from (77.34±12.20) to (64.59±15.60) (P=0.005) while memory B cells increased from (21.79±11.97) to (34.21±15.48) (P=0.006) respectively. The concentrations of TNF-α and IFN-γ decreased in the TGP group at week 24 from (32.51±26.67) to (24.22±13.56) (P=0.017) and (10.71±8.94) to (6.55±4.88) (P=0.022), respectively. No significant difference in ANA titer, anti-SSA antibodies, anti-SSB antibodies, C3 concentration or C4 concentration was observed between the two groups. ConclusionTGP appears to improve the glandular secreting function and decrease the level of inflammatory cytokines.

Analysis of Clinical Factors Associated with Retinal Morphological Changes in Patients with Primary Sjögren's Syndrome.

PurposeTo investigate clinical factors associated with abnormal retinal morphologies in patients with primary Sjögren's syndrome (pSS).MethodsOne-hundred-thirty patients with pSS who underwent immunoserological tests, minor salivary gland biopsies, and optical coherence tomography examinations were retrospectively analyzed. Risk factors for abnormally reduced peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell–inner plexiform layer (mGCIPL) thicknesses were evaluated, as well as the correlation between clinical factors and pRNFL and mGCIPL thicknesses.ResultsAnti-Sjögren's syndrome type B (SSB) antibody positivity (P = 0.048) was identified as a risk factor associated with abnormally reduced pRNFL thickness, and anti-SSB positivity (P = 0.005) and erythrocyte sedimentation rate (ESR) level (P = 0.031) were identified as risk factors associated with an abnormally reduced mGCIPL thickness as revealed by multivariate logistic regression analysis. There was a significant negative correlation between anti-SSB antibody levels and the thickness of pRNFL and mGCIPL. The thicknesses of pRNFL and mGCIPL were significantly reduced in anti-SSB–positive eyes when compared to anti-SSB–negative eyes (P < 0.05). However, histopathologic grading was not associated with the pRNFL and mGCIPL thicknesses.ConclusionAnti-SSB antibody positivity and ESR levels may be useful for predicting an abnormally reduced pRNFL or mGCIPL thickness in patients with pSS. Our results may provide clinical evidence to substantiate the association between aberrant autoimmunity and inner retinal changes in patients with pSS.

Anterior horn syndrome: A rare manifestation of primary Sjögren's syndrome

The authors report an exceptional case of an anterior horn syndrome associated with Sjögren's syndrome in a 58-year-old patient with a flaccid tetraparesis revealed by asymmetric atrophy and diffuse fasciculations associated with xerostomia and xerophthalmia. The electroneuromyography objectified a diffuse anterior horn syndrome. The brain MRI and spinal cord were normal. Laboratory tests revealed positive anti-SSA and anti-SSB antibody. The salivary glands biopsy objectified lymphocytic sialadenitis grade 3 of Chisholm. The Schirmer's test was abnormally low. Diagnosis of anterior horn syndrome as part of Sjögren's syndrome was retained. The methylprednisolone bolus allowed partial clinical improvement after 12 months of evolution. Therefore, in patients with isolated anterior horn involvement, a correct diagnosis of the underlying SS is often delayed or overlooked entirely; in these instances, standard clinicoserological assessment is recommendable.

Epitope spreading induced by immunization with synthetic SSB peptides.

Sjogren's syndrome type B (SSB)/La antibody is an autoantibody generally observed in connective tissue diseases whereas double-stranded deoxyribonucleic acid (dsDNA) antibodies are the most characteristic autoantibodies found in systemic lupus erythematosus (SLE) patients. The relationship of these autoantibodies remains unclear. The aim of the study was to determine the profile of antibody production in rabbits immunized with synthetic SSB peptides alone or with dsDNA. For this purpose, 214–225aa peptide of SSB antigen was synthesized based on the organic chemistry solid-phase peptide synthesis. Rabbits were immunized with the following antigens: i) synthetic SSB peptides linked with keyhole limpet hemocyanin (KLH); ii) dsDNA; iii) SSB plus dsDNA; iv) KLH; and v) phosphate-buffered saline. SSB peptide antibody was measured using the enzyme-linked immunosorbent assay while extractable nuclear antigens (ENA) antibody and dsDNA antibody were measured by immunoblotting and immunofluorescence, respectively. The results showed that a specific anti-SSB peptide antibody was produced following immunization with SSB epitope alone or with dsDNA. The SSB peptide antibody titer in the coimmunization group was higher than that of the SSB alone group. In addition, antibodies against ribonucleoprotein (RNP), Smith and/or dsDNA were detected in rabbits of the coimmunization group. The presence of anti-dsDNA antibodies in the rabbits immunized with SSB peptide suggested the induction of epitope spreading. In conclusions, SSB antibodies were produced in rabbits immunized with SSB peptide or SSB+dsDNA, whereas SSB antibody titers were higher in the coimmunization group. Furthermore, coimmunization was associated with epitope spreading.

Audiological Profile in Primary Sjögren's Syndrome in a Tertiary Care Setting and its Clinical Implications.

This study aims to assess the frequency and the profile of hearing loss among patients with primary Sjögren's syndrome in a tertiary care hospital in India and to look for an association between hearing loss and immunological parameters (anti-SSA antibody, anti-SSB antibody, anticardiolipin antibodies, complements C3 and C4). This prospective observational study was done from January 2011 to October 2011 on consecutive patients diagnosed with primary Sjögren's syndrome in our tertiary care hospital. All patients underwent a puretone audiogram, tympanogram and acoustic reflex testing. The results of the tests were correlated with clinical and immunological findings. The frequency of audiometrically confirmed hearing loss in primary Sjögren's syndrome was estimated to be 78.38%, though only 17.24% complained of hearing loss; minimal to mild sensorineural hearing loss were the most common varieties. The commonest finding on tympanometry was 'A' type curve and acoustic reflex was absent in 18.92% of cases. There was no association between hearing loss and age, sicca symptoms, systemic symptoms or immunological test results in primary Sjögren's syndrome. There was a high prevalence of hearing loss among patients with primary Sjögren's syndrome, but most patients were unaware of this. Hearing assessment and regular monitoring of hearing thresholds is advisable for all patients with primary Sjögren's syndrome.

Multiple osteoporotic fractures in a patient with CKD stage G3b

A previously healthy 54-year-old Japanese woman presented with pain in her right chest and left inguinal area after lifting a heavy object. She also had left chest pain 4 months earlier associated with coughing. She was not obese, and her blood pressure was 104/56 mm Hg. On physical examination, she had bilateral rib tenderness and otherwise normal results. Chest X-rays revealed multiple healing rib fractures, and bone scintigraphy showed increased uptake in the left pelvic bone and bilateral ribs (Figure 1). Her blood cell counts were normal. The blood laboratory findings were as follows: total protein, 7.3 g/dl; albumin, 3.8 g/dl; creatinine, 1.35 mg/dl (estimated glomerular filtration rate 32.8 ml/min per 1.73 m2); sodium, 137 mEq/l; potassium, 3.3 mEq/l; chloride, 110 mEq/l; calcium, 8.7 mg/dl; phosphorus, 2.5 mg/dl; alkaline phosphatase, 418 U/l; intact parathyroid hormone, 85 pg/ml; and venous HCO3−, 21 mmol/l. The urinalysis showed a pH of 6.5 and negative findings for blood, protein, and sugar. The urinary Bence Jones protein was negative. Sonography showed atrophy of the bilateral kidneys, with a size of 8.5 cm. An arterial blood-gas analysis revealed the following values: pH, 7.34; PCO2, 36 mm Hg; PO2, 87 mm Hg; and HCO3−, 19 mmol/l. She showed a positive response for the antinuclear antibody test, with a normal complement level. She also showed positive test results for anti-SSA and anti-SSB antibodies, positive criteria for Schirmer’s test, and focal lymphocytic sialoadenitis in a lip biopsy. She was diagnosed as having Sjogren syndrome with renal tubular acidosis (RTA), and a renal biopsy was performed (Figure 2). After treatment with corticosteroids and potassium citrate combined with sodium citrate, her symptoms disappeared and her renal function improved. Distal RTA should be considered in patients with hyperchloremic metabolic acidosis and multiple bone fractures.

Clinical and laboratory profiles of primary Sjogren's syndrome in a Chinese population: A retrospective analysis of 315 patients.

To assess the clinical and laboratory features of primary Sjogren's syndrome (pSS) in a large teaching hospital in China. Three hundred and fifteen pSS patients diagnosed according to American-European Classification Criteria and consecutively admitted to Anhui Provincial Hospital from 1 January 1999 to 30 September 2012 were retrospectively selected in this study. The median age was 46.8 ± 14.4 years (range 13-83 years) and the majority of patients were female (96.5%). The common clinical features at initial presentations were dry mouth (50.2%), dry eyes (31.4%) and joint pain (24.8%); 92.6% of patients had positive anti-SSA antibody and 49.2% patients had positive anti-SSB antibody. One hundred and eighteen patients underwent labial salivary gland biopsy. According to Chisholm grading criteria, grade 3 to 4 was present in 58.5% of the patients. The frequency of interstitial lung disease (ILD) occurred (20.9%) in the patients with systemic extraglandular manifestations. The patients with ILD were frequently associated with positive anti-SSA (P = 0.005) and low levels of C3. The most common impairment of lung function was small airway function abnormalities. Sixty-six pSS patients with ILD (pSS-ILD) were diagnosed with high-resolution computed tomography and treated with corticosteroids and/or immunosuppressants, in which 18 patients had improved pulmonary function. Labial salivary gland biopsy and anti-nuclear antibodies spectrum were important to the diagnosis of pSS. The pSS patients had high percentage of ILD, especially small airway function abnormalities. The combination of corticosteroids and immunosuppressants appears to be effective in treatment of pSS patients with ILD.

STAT-5 is activated constitutively in T cells, B cells and monocytes from patients with primary Sjögren's syndrome.

The expression and phosphorylation of signal transducer and activator of transcription-1 (STAT-1) have been shown to be markedly increased in the salivary gland epithelial cells of patients with primary Sjögren's syndrome (pSS). The present aim was to investigate the activation status of different STAT proteins in peripheral blood (PB) lymphocytes and monocytes, and their correlations with clinical parameters in patients with pSS. To this end, PB samples were drawn from 16 patients with active pSS and 16 healthy blood donors, and the phosphorylation of STAT-1, -3, -4, -5 and -6 proteins was studied in T cells, B cells and monocytes using multi-colour flow cytometry. In addition, mRNA expression of STAT molecules in PB mononuclear cells (PBMC) was studied with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Basal phosphorylation of STAT-5 was found to be significantly higher in PB T cells, B cells and monocytes in patients with pSS than in healthy controls. The expression of STAT-5 mRNA was not increased in PBMC. pSTAT-5 levels in B cells and monocytes showed a significant correlation with serum immunoglobulin (Ig)G levels and anti-SSB antibody titres. Constitutive STAT-5 activation in monocytes and CD4(+) T cells was associated with purpura. There were no major differences in the activation of other STATs between pSS patients and healthy controls. In conclusion, STAT-5 is activated constitutively in PB leucocytes in patients with pSS, and basal STAT-5 phosphorylation seems to associate with hypergammaglobulinaemia, anti-SSB antibody production and purpura.

Decreased UBASH3A mRNA Expression Levels in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus.

Increasing evidence has demonstrated the association between UBASH3A gene and multiple autoimmune diseases (ADs). The aim of our study was to explore the potential effect of UBASH3A messenger RNA (mRNA) expression and its role in the pathogenesis of systemic lupus erythematosus (SLE). UBASH3A mRNA levels were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in total RNA, isolated from the peripheral blood mononuclear cells (PBMCs) of 32 SLE patients and 30 healthy donors with TRIzol Reagent. The expression level of UBASH3A mRNA was significantly reduced in PBMCs from SLE patients when compared with healthy controls (p = 0.002). UBASH3A mRNA expression levels in lower active SLE were significantly lower than that in inactive SLE groups (p = 0.000). There was a negative association between mRNA levels of hyper-active and lower-active SLE patients (p = 0.000). Moreover, a significant negative correlation between UBASH3A mRNA expression and the onset age of SLE patients was found (p = 0.044). A negative correlation was found between UBASH3A mRNA expression and SLEDAI (p = 0.049). Nevertheless, no significant difference was found between patients with lupus nephritis (LN) and those without LN (p = 0.392). The presence of leukopenia, positive for anti-dsDNA antibody and anti-SSB antibody were associated with UBASH3A mRNA levels in SLE patients (all p < 0.05). The dysregulation of UBASH3A mRNA levels in SLE patients and their correlations with experimental parameters suggested that UBASH3A may involve in the pathogenesis of SLE.

The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sjögren's syndrome

ObjectiveTo determine whether the Sjögren's syndrome B (SSB)-positive/Sjögren's syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS.MethodsAmong registrants in the Sjögren's International Collaborative Clinical Alliance (SICCA)...