The Impact of Vitamin D on Cognitive Dysfunction in Mice with Systemic Lupus Erythematosus.

BACKGROUND A growing body of evidence suggests that systemic lupus erythematosus (SLE) may result in reversible cognitive dysfunction. Vitamin D is considered important for neurons. The therapeutic effect of vitamin D was evaluated in a rat model of SLE. MATERIAL AND METHODS There were 20 male MRL/lpr mice randomly divided into the SLE model group and the vitamin D group, in addition, 10 male C57BL 6J mice were used as the control (CON) group. Vitamin D was administered intraperitoneally (2 µg/kg) for 4 weeks. After 4 weeks of continuing intervention, we tested the cognitive function using the Morris water maze. The expression of vitamin D receptor (VDR), amyloid-ß, caspase-3, and Bcl-2 were detected by western blot analysis. RESULTS In the present study, we observed that vitamin D treatment alleviated neurobehavioral deficits in the mice with SLE. At the molecular levels, administration of vitamin D activated the expression of VDR and reduced the number of dead cells in the CA1 region of the hippocampus as well as regulated caspase-3 and Bcl-2 expression. CONCLUSIONS In conclusion, our results indicated that vitamin D played a protective role by suppressing inflammatory cytokines, thereby ultimately inhibiting the progression of apoptosis in a mouse model of SLE. Vitamin D may be promising as a protective intervention in SLE with cognitive dysfunction, and more and more experiments are warranted for its clinical testing in the near future.

A retrospective study of patients with systemic lupus erythematosus combined with Pneumocystis jiroveci pneumonia treated with caspofungin and trimethoprim/sulfamethoxazole.

Systemic lupus erythematosus (SLE) complicated with Pneumocystis jiroveci pneumonia (PCP) is a clinical complex with unsatisfying treatment efficacy and poor prognosis which is difficult to be diagnosed at early stage. The present study aimed to investigate the clinical features of SLE with PCP, recognize the early onset indicating factors, and evaluate the treatment efficacy of combined caspofungin and trimethoprim/sulfamethoxazole (coSMZ).We reviewed data of 9 patients admitted with SLE-PCP and treated with caspofungin combined with coSMZ at Tangshan Gongren Hospital from January 2013 to December 2017. Patients' clinical manifestation and laboratory data [leucocyte, lymphocyte, cluster of differentiation 4 (CD4)T cell, lactate dehydrogenase (LDH), blood gas, etc] were compared before and after treatments. And the early onset factors of SLE-PCP, treatment efficacy of combined caspofungin and CoSMZ were analyzed.Among these 9 patients, 8 patients suffered renal impairment, and all of them had been taking prednisone in the past 3 months at an average dose of 29.4 ±â€Š13.6 mg/day. In addition, they had taken at least one kind of immunosuppressants. Laboratory data (leucocyte, lymphocyte, CD4T cell, PaO2, LDH) were remarkably abnormal at hospital admission, but they were improved significantly after 2 weeks of treatment, which is also statistically significant (P < .05), except that leukocyte had no significance change to the value at admission (P = .973). In addition, none of the studied patients died.The results of the study indicated that long-term use of glucocorticoids and immunosuppressants, low CD4T cell count, and renal impairment are the early-onset factors for SLE-PCP, caspofungin, when combined with CoSMZ, it could be a promising and effective strategy to treat SLE with PCP.

A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23.

Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.

Specificity of anti-SSB as a diagnostic marker for the classification of systemic lupus erythematosus.

The aim of the present study was to investigate the sensitivity and specificity of anti-Sjögren's syndrome type B (SSB) antibodies for diagnosing systemic lupus erythematosus (SLE) and to understand the correlation between anti-SSB antibodies and the clinical manifestations of SLE. A line immunoassay (LIA) was used to detect the presence of serum anti-SSB antibodies in SLE patients. The clinical manifestations of the patients were recorded to enable their correlation with the serum anti-SSB antibodies to be analyzed. In 25.7% of the 74 SLE patients, the serum was positive for anti-SSB antibodies, whereas only 3.3% of the 30 control cases were positive. The specificity of anti-SSB antibodies for detecting SLE was 96.7%. In anti-SSB antibody-positive SLE patients, the incidence of cheek erythema, alopecia, serositis, secondary Sjögren's syndrome (sSS), leukocytopenia, elevated immunoglobulin (Ig)G and positive presence of anti-Sjögren's syndrome type A (SSA)60 or anti-SSA52 antibodies was higher than in the anti-SSB antibody-negative group (P<0.05). Anti-SSB antibodies are important for the diagnosis of SLE and are associated with cheek erythema, alopecia, serositis, sSS, leukocytopenia, the elevation of IgG and positive presence of anti-SSA60 or anti-SSA52 antibodies.

[Value of bronchoalveolar lavage as a rescue measurement for systemic lupus erythematosus complicated with diffuse alveolar hemorrhage].

OBJECTIVE: To explore the value of bronchoalveolar lavage as an emergency treatment for systemic lupus erythematosus (SLE) patients with concurrent diffuse alveolar hemorrhage (DAH). METHODS: A total of 21 SLE plus DAH patients were divided randomly into 2 groups. The patients in Group A received methylprednisolone 1000 mg/d for 3 days while those in Group B methylprednisolone 1000 mg/d for 3 days in combination with a bronchoalveolar lavage. Partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), oxygen saturation (SaO2) and Borg scale (BS) for quantitative evaluation of dyspnea were recorded before and after treatment. RESULTS: Except for PaCO2, all other parameters of blood gas analysis in all patients in Group A (P > 0.05) were better after treatment than before (all P < 0.05). After treatment, PaO2 and SaO2 in Group B were higher than those in Group A (all P < 0.05), but PaCO2 was not markedly changed (P > 0.05). BS decreased significantly in both groups (both P < 0.01). And more decrease was observed in Group B as compared with Group A after treatment (P < 0.05). CONCLUSION: Bronchoalveolar lavage plus a high-dose implosive therapy of methylprednisolone may alleviate hypoxemia and dyspnea in acute period of SLE complicated with DAH.

[Detection of anti-SSA/Ro antibody by ELISA, double immunodiffusion, and immunoblotting: a comparative study].

OBJECTIVES: To compare the specificity and sensitivity of ELISA, double immunodiffusion (ID), and immunoblotting (IB) in detection of anti-SSA/Ro antibodies in the sera of patients with connective tissue disease (CTD). METHODS: ELISA, double ID, and IB were used to detect the serum levels of anti-SSA/Ro antibodies in 7736 patients undergoing screening of CTD, 122 healthy blood donors, and 166 CTD patients positive in antinuclear antibody (ANA) and/or anti-extractable nuclear antigen (ENA). RESULTS: (1) The sera of the 122 healthy blood donors were all negative in anti-SSA/Ro antibodies by these three methods. (2) 1085 of the 7736 sera undergoing screening of CTD were positive in the anti-SSA/R0 antibody of the relative molecular quantity of 52,000. Ninety-two of the 1085 patient, ANA and/or anti-ENA negative, were all confirmed by ELISA and ID to be negative in anti-SSA/R0 antibodies. And 993 of these 1085 patients were positive in ANA and/or anti-ENA antibody, 917 of which were shown to be anti-SSA/R0 antibodies positive by ELISA (92.3%, 917/993), and 860 of which were shown to be anti-SSA/R0 antibodies positive by ID (86.6%, 860/993). (3) The prevalence rates of anti-SSA/Ro antibodies in the 166 CTD patients detected by ELISA, ID, and IB respectively were 76.5% (127/166), 65.1% (108/166), and 49.4% (82/166) respectively. (4) 127 of the 166 sera of the CTD group were anti-SSA/Ro antibody positive By ELISA, and 108 of the 166 sera were anti-SSA/R0 antibody positive by ID, with a coincidence rate of ELISA and ID of 88.6% (147/166), and there was a significant difference in positive rate of anti-SSA/Ro antibody between these two methods (P < 0.001). 81 of the 166 CTD sera were anti-SSA/Ro antibody positive with a positive rate of 63.8%. The coincidence rate of ID and IB was 75.9% (126/166) and there was a significant difference in positive rate of anti-SSA/Ro antibody between ID and IB methods too (P < 0.001). (5) Spearman's rank correlation study showed that the correlation coefficient between ELISA and ID was 0.828 (P < 0.001). CONCLUSIONS: (1) ELISA and ID are more specific than IB in detection of anti-SSA/Ro antibody. (2) The specificity of IB was lower, however, when ANA and/or other anti-ENA are positive, its specificity would be improved markedly. (3) ELISA is more sensitive than ID, and ID is more sensitive than IB in detection of anti-SSA/Ro antibody. (4) There is a significant positive correlation between ELISA and ID quantitatively.

[Characteristics of airway involvement in relapsing polychondritis].

OBJECTIVE: To investigate the characteristics of airway involvement in relapsing polychondritis (RP). METHODS: The clinical data, including clinical manifestations, respiratory function test, computerized tomography (CT), and bronchoscopy of 38 out of the 56 RP patients who had airway involvement, 20 males and 18 females, with the mean onset age of 45 +/- 11 (27 - 71), and 3 RP patients without airway involvement were retrospectively analyzed. Three patients out of the 16 RP patients who did not have respiratory involvement but underwent respiratory function test, CT, and bronchoscopy were used as controls. RESULTS: The symptoms of airway involvement included cough, expectoration, hoarseness, feeling of suffocation, asthma, and dyspnea. Obstructive disturbance of ventilation was found in 10 and mixed disturbance of ventilation was seen in 2 of the 18 RP patients with airway involvement. The forced expiratory volume in one second, ratio of forced expiratory volume in one second to forced vital capacity, peak expiratory flow, FEF50/FIF50, and maximal mild-expiratory flow of the patients with airway involvement were 1.4 L +/- 0.23 L, 46.0 +/- 4.86, 3.3 L/s +/- 0.67 L/s, 0.3 +/- 0.08, and 0.4 L/s +/- 0.18 L/s respectively, all significantly lower than those of the RP patients without airway involvement (2.5 L +/- 0.09 L, 83.7 +/- 2.24, 6.9 L/s +/- 0.52 L/s, 1.3 +/- 0.51, and 2.8 L/s +/- 0.73 L/s, all P = 0.01). Flow volume loop showed remarkable decrease of PEF and formation of a plateau in the expiratory phase in the RP patients with airway involvement. CT performed in 27 RP patients with airway involvement showed trachea stenosis in 11, and thickened airway wall in 8 of them. Bronchoscopy performed in 23 patients with airway involvement showed inflammation in 16, destruction of tracheobronchial cartilage in 6, collapsed tracheobronchial wall in 7, tracheal stenosis in 15, left major bronchial stenosis in 13, and right major bronchial stenosis in 12 of them. CONCLUSION: Respiratory function test is sensitive in early detection of airway involvement in RP. Bronchoscopy and CT are useful in evaluation of the severity of airway involvement in patients with RP.

[Clinical analysis of pneumomediastinum complicated in polymyositis and dermatomyositis].

OBJECTIVE: To analyze the clinical features of pneumomediastinum complicated in polymyositis and dermatomyositis (PM/DM) and to study the pathogenesis thereof. METHODS: The clinical data of 4 patients with pneumomediastinum complicated in dermatomyositis out of 447 PM/DM patients hospitalized in Peking Union Medical College (PUMC) Hospital Jan 1989 to June 2005, were analyzed. The records of patients with PM/DM available in English throughout the world were reviewed to collect those with pneumomediastinum as a complication. And the data of these patients were analyzed, focusing mainly on the age, gender, peak of serum creatine kinase (CK), presence of pneumomediastinum, cutaneous vasculopathy, chest radiographic changes, tracheal cannula, management, and outcome. RESULTS: Among the 447 patients with PM/DM hospitalized in PUMC Hospital, 134 males and 313 females, aged 42 +/- 17, pneumomediastinum was observed as a complication in four patients, 3 males and 1 female, aged 12 - 43, with a prevalence rate of 0.9%. Together with 17 cases reported in the English literatures there were 21 patients with pneumomediastinum complicated in polymyositis and dermatomyositis (PM/DM in all. Only one of the literatures reported a prevalence rate as high as 8.3% (4/48), and other literatures were merely case reports. Compared with the PM/DM patients without pneumomediastinum the mean age of the PM/DM patients with pneumomediastinum was significantly younger (34:42, P < 0.01), the male: female ratio significantly higher (13:8 to 132:311, P < 0.01), the morbidity rates of interstitial lung disease and of cutaneous vasculopathy significantly higher (18/21 to 134/443, and 12/21 to 44/443, both P < 0.01). Although statistic analysis could not be undertaken because of the peak of CK not being provided in details in the literatures, the CK levels of the patients with pneumomediastinum were mostly normal or mildly higher with a peak lower than 500 U/L Three of the 4 patients with pneumomediastinum hospitalized in PUMC Hospital and 5 of the 443 patients (1.1%) without this complication received tracheal cannula. There was a significant association of pneumomediastinum with tracheal cannula (P = 0.000). CONCLUSION: Vasculopathy is strongly suspected as being responsible for the pneumomediastinum in DM, and male gender, younger age, interstitial lung disease, and tracheal cannula may be the risk factors of this pneumomediastinum complicated in PM/DM.