Outcomes following total shoulder arthroplasty in patients with systemic lupus erythematosus.

BACKGROUND: Total shoulder arthroplasty (TSA) is a common procedure that may be considered for patients with glenohumeral osteoarthritis. Patients undergoing this procedure may be afflicted by comorbid conditions, such as systemic lupus erythematosus (SLE), which may impact odds of various postoperative complications. METHODS: Adult patients with and without SLE who underwent TSA (anatomic or reverse) were queried from the Jan 2010 to Oct 2022 PearlDiver M165 database. Patients with and without SLE were matched (1:4) based on age, sex, and Elixhauser Comorbidity Index. Ninety-day adverse events and five-year implant survival were assessed and compared with multivariable analysis. Sub-analyses were done for SLE patients with and without a prescription of immunomodulatory therapy (IMT - corticosteroids, hydroxychloroquine, and/or biologics) within 90 days prior to surgery and compared to non-SLE patients with multivariable analyses. Lastly, SLE patients with and without a 90-day history of IMT were directly compared with multivariate logistic regression. A Bonferroni correction was applied to univariable analyses and multivariable regressions. RESULTS: Of 211,832 TSA patients identified, SLE was noted for 2,228 (1.1%). After matching, 8,261 patients without SLE and 2,085 patients with SLE were selected. SLE patients were at an increased odds of 90-day aggregated events including severe (OR=3.50), minor (OR=3.13), all (OR=2.35), and orthopedic-related (OR=1.41) adverse events (p<0.0030 for all). There was no difference in 5-year implant survival. Of those with SLE, IMT medications were being received by 1,267 (60.8%). Any, severe, minor, and orthopedic 90-day adverse events were significantly elevated for both those with and without IMT relative to those without SLE (p<0.0030 for all except for orthopedic-related adverse events for those not on IMT which were not significant). Relative to those not on IMT medications, those on IMT medications were at significantly higher odds of any, severe, minor, and orthopedic-related adverse events. CONCLUSION: Following TSA, patients with SLE were found to be at an increased odds of 90-day adverse events but not of 5-year revisions. Furthermore, those on IMT medications were at higher risk of any, severe, minor, and orthopedic-related adverse events compared to those who were not on these medications. These findings may help with patient counselling and surgical planning when those with SLE are considered for TSA.

Endocrine-disrupting chemicals and autoimmune diseases.

Endocrine-disrupting chemicals (EDCs) widely exist in people's production and life which have great potential to damage human and animal health. Over the past few decades, growing attention has been paid to the impact of EDCs on human health, as well as immune system. So far, researchers have proved that EDCs (such as bisphenol A (BPA), phthalate, tetrachlorodibenzodioxin (TCDD), etc.) affect human immune function and promotes the occurrence and development of autoimmune diseases (ADs). Therefore, in order to better understand how EDCs affect ADs, we summarized the current knowledge about the impact of EDCs on ADs, and elaborated the potential mechanism of the impact of EDCs on ADs in this review.

LRRK2 is involved in the pathogenesis of system lupus erythematosus through promoting pathogenic antibody production.

BACKGROUND: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the presence of pathogenic autoantibodies associated with polyclonal B cell hyperreactivity. Previous study reported that autophagy-related gene Leucine-rich repeat kinase 2 (LRRK2) was likely a susceptible gene for SLE. However, the pathogenic function of LRRK2 in SLE is undefined. METHODS: Using quantitative PCR, we compared the expression levels of LRRK2 in B cells between SLE patients and healthy controls. The expression levels of LRRK2 in in vitro induced CD19hi B cells and naïve B cells were compared as well based on RNA-seq assay. A pristane-induced lupus-like mouse model was used to explore the effects of LRRK2 on the development of SLE. IgG level, B cell subsets in the spleens and bone marrows and pathological features in the kidneys were compared between wildtype (WT) and Lrrk2-/- littermates. RESULTS: It was obvious that LRRK2 expression was dramatically up-regulated in primary B cells from SLE patients compared to those from healthy controls, as well as in activated CD19hi B cells. More significantly, LRRK2 expression in B cells was positively correlated with system lupus erythematosus disease activity index (SLEDAI), an indicator for disease severity, and serum IgG levels in SLE patients. Negative correlations were observed between LRRK2 expression and serum C3 or C4 levels, two clinical features associated with SLE-related nephritis. LRRK2 deficiency reduced the death rate of pristane treated mice. Decreased levels of total IgG and autoantibody were detected in the serum with less deposition of immune complexes and attenuated pathological symptoms in the kidneys of Lrrk2-/- mice. Consistent with the reduction in IgG production, the percentages of germinal center B cells and plasma cells decreased significantly as well with LRRK2 deficiency. CONCLUSIONS: Our study demonstrates that LRRK2 expression is upregulated in B cells from SLE patients with strong correlations to disease severity. LRRK2 deficiency largely attenuates the pathogenic progress of lupus-like features in pristane-induced mice. This is probably achieved through affecting B cell terminal differentiation and subsequent immunoglobulin production.

[Correlation of Thyroid Autoantibodies,System Lupus Erythematosus Immunologic Indicators and Disease Activity in SLE with HT].

OBJECTIVE: To investigate the correlation of disease activity and thyroid indicators ,immunologic markers of system lupus erythematosus (SLE) in SLE with Hashimoto's thyroiditis (HT). METHODS: The clinical data of 63 cases of SLE with HT were collected. According to Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2000),we classified the patients into four groups,which were remission group (5 cases),low (19 cases),moderate (12 cases) and high (27 cases) disease activity group. Each patient received the measurement of thyroid function indicators and autoantibodies,SLE immunologic indicators,serum complement (C3,C4),C-reactive protein (CRP),erythrocyte sedimentation rate (ESR), and routine blood test. The correlation of thyroid indicators,immunologic markers and disease activity were analyzed. RESULTS: The difference of free triiodothyronine (FT3) level in the four groups was statistically significant (P<0.05),and FT3 was negatively correlated with SLE disease activity (P=0.007) . There was no significant difference in other thyroid indicators and autoantibodies between the different groups (P>0.05). Negative correlation was found between FT3 level and anti-double-stranded DNA (dsDNA),level of anti-La antibody (SSB) and thyroid stimulating hormone (TSH) or thyroid peroxidase antibody (TPOAb). Thyroglobulin autoantibody (TgAb) was negatively related with C4,and positive correlation between FT3 and C3,FT4 and C4,TgAb and IgA. CONCLUSION: The pathogenesis of HT is associated with the disease activity in the patients of SLE with HT.

The prognosis and management of reclassified systemic lupus erythematosus associated pulmonary arterial hypertension according to 2022 ESC/ERS guidelines.

BACKGROUND AND AIMS: The 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guideline has recently revised the hemodynamic definition of pulmonary arterial hypertension. However, there is currently limited research on the prognosis and treatment of system lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) patients that have been reclassified by the new hemodynamic definition. This study aims to analyze the prognosis of newly reclassified SLE-PAH patients and provide recommendations for the management strategy. METHODS: This retrospective study analyzed records of 236 SLE-PAH patients who visited Peking Union Medical College Hospital (PUMCH) from 2011 to 2023, among whom 22 patients were reclassified into mild SLE-PAH (mean pulmonary arterial pressure (mPAP) of 21-24 mmHg, pulmonary vascular resistance (PVR) of 2-3 WU, and PAWP ≤ 15 mmHg) according to the guidelines and 14 were defined as unclassified SLE-PAH patients (mPAP 21-24 mmHg and PVR ≤ 2 WU). The prognosis was compared among mild SLE-PAH, unclassified SLE-PH, and conventional SLE-PAH patients (mPAP ≥ 25 mmHg and PVR > 3WU). Besides, the effectiveness of pulmonary arterial hypertension (PAH)-specific therapy was evaluated in mild SLE-PAH patients. RESULTS: Those mild SLE-PAH patients had significantly longer progression-free time than the conventional SLE-PAH patients. Among the mild SLE-PAH patients, 4 did not receive PAH-specific therapy and had a similar prognosis as patients not receiving specific therapy. CONCLUSIONS: This study supports the revised hemodynamic definition of SLE-PAH in the 2022 ESC/ERS guideline. Those mild and unclassified SLE-PH patients had a better prognosis, demonstrating the possibility and significance of early diagnosis and intervention for SLE-PAH. This study also proposed a hypothesis that IIT against SLE might be sufficient for those reclassified SLE-PAH patients.

Non-scarring patchy alopecia in patients with systemic lupus erythematosus differs from that of alopecia areata.

BACKGROUND: Non-scaring patchy alopecia associated with systematic lupus erythematosus (SLE) is sometimes mis-diagnosed as alopecia areata (AA). OBJECTIVES: Our aim was to differentiate non-scarring patchy SLE alopecia features from patchy AA. METHODS: Clinical, dermatoscopic and histopathological data from 21 SLE patients with patchy alopecia were compared with data from 21 patients with patchy AA. RESULTS: Incomplete alopecia was common in SLE alopecia patches, while AA patches exhibited complete alopecia. Exclamation-mark hairs, black dots, broken hair and yellow dots were common to AA, while hair shaft thinning and hypopigmentation, angiotelectasis, peripilar sign, perifollicular red dots, white dots and honeycomb pigment patterns were more common in SLE. Interfollicular polymorphous vessels were the most common angiotelectasis presentation in the SLE alopecia patches, but interfollicular arborizing vessels were significantly more common in non-hair-loss-affected SLE regions and in AA hair-loss regions. During follow-up, increased vellus hair was the earliest feature that emerged after treatment both in SLE and AA, while the earliest feature that disappeared was hair shaft hypopigmentation in SLE and broken hair in AA. After treatment, no SLE patients had relapse of alopecia, while 41.7% of AA patients did. CONCLUSION: Distinct clinical, dermatoscopic and histopathological features were found in SLE-associated alopecia regions, which were different from those of AA. Serological autoantibody tests are of value to confirm the differential diagnosis. Local angiotelectasis and vasculitis close to hair follicles may be involved in the pathogenesis of alopecia in SLE.

Exploring the potential common denominator pathogenesis of system lupus erythematosus with COVID-19 based on comprehensive bioinformatics analysis.

Objective: Evidences show that there may be a link between SLE and COVID-19. The purpose of this study is to screen out the diagnostic biomarkers of systemic lupus erythematosus (SLE) with COVID-19 and explore the possible related mechanisms by the bioinformatics approach. Methods: SLE and COVID-19 datasets were extracted separately from the NCBI Gene Expression Omnibus (GEO) database. The limma package in R was used to obtain the differential genes (DEGs). The protein interaction network information (PPI) and core functional modules were constructed in the STRING database using Cytoscape software. The hub genes were identified by the Cytohubba plugin, and TF-gene together with TF-miRNA regulatory networks were constructed via utilizing the Networkanalyst platform. Subsequently, we generated subject operating characteristic curves (ROC) to verify the diagnostic capabilities of these hub genes to predict the risk of SLE with COVID-19 infection. Finally, a single-sample gene set enrichment (ssGSEA) algorithm was used to analyze immune cell infiltration. Results: A total of 6 common hub genes (CDC6, PLCG1, KIF15, LCK, CDC25C, and RASGRP1) were identified with high diagnostic validity. These gene functional enrichments were mainly involved in cell cycle, and inflammation-related pathways. Compared to the healthy controls, abnormal infiltration of immune cells was found in SLE and COVID-19, and the proportion of immune cells linked to the 6 hub genes. Conclusion: Our research logically identified 6 candidate hub genes that could predict SLE complicated with COVID-19. This work provides a foothold for further study of potential pathogenesis in SLE and COVID-19.

Intestinal fungi and systemic autoimmune diseases.

Nearly 20 years of studies have shown that fungi and the human immune system (non-specific immunity and specific immunity) and bacterial--fungal interactions maintain a balance that can't lead to diseases. Fungi--microorganism that lives in human intestine--may play an important role in human health and disease. Population studies and animal models in some diseases have found the changes in the diversity and composition of fungi. The dysregulation of the fungi can disrupt the normal "running" of the immune system and bacteria, which triggers the development of inflammatory diseases. The latest studies of fungi in inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and type 1 diabetes mellitus were summarized. This review considers how the healthy host protect against the potential harm of intestinal fungi through the immune system and how fungal dysregulation alters host immunity.

[Anxiety-depressive disorders and stress factors in patients with systemic lupus erythematosus and antiphospholipid syndrome]. / Osobennosti rasstroistv trevozhno-depressivnogo spektra i stressovykh faktorov u bol'nykh sistemnoi krasnoi volchankoi i antifosfolipidnym sindromom.

OBJECTIVE: The aim of this work was to analyze the frequency and, spectrum of mental disorders (MD), and stressful factors, as well as the characteristics of anxiety and depressive spectrum disorders (ADSD) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: The study included 155 patients (37 (23.9%) men and 118 (76.1%) women) aged 18 to 69 years ((M±SD) 37.7±12.3 years), including. 61 (39.3%) patients - with a reliable diagnosis of SLE according to the 2019 EULAR/ACR criteria, 48 (30.9%) patients with - SLE with secondary APS and 46 (29.7%) - with primary APS (PAPS), established according to the international criteria of 2006. RESULTS: The majority of the examined patients were found to hadve MD (current MD in 145 (93.5%) patients). ADSD prevailed in all groups: in 58 (95.1%) patients with SLE, in 42 (87.5%) - with SLE with APS and in, 39 (84.8%) - with APS. Patients with SLE were exposed to stressful events in childhood (predominantly parental deprivation) more often than patients with SLE with APS and PAPS were exposed to stressful events in childhood (93.4% versus 81.2% and 69.6%, respectively; predominantly parental deprivation). ADSD in these patients developed mainly in pre-adolescence, with a tendency towards chronic variants without remission, which leads to a greater vulnerability of the patients in this group to stressful events compared with patients with APS (p=0.05). CONCLUSION: When diagnosing and treating MD in patients with SLE and APS, special attention should be paid to the analysis of the history of stressful eventsstress history of patients, which affects the formation of common predisposing and provoking factors, both MD and RD, aggravating their course and prognosis.

Plasma galectin-3 levels do not differ in systemic lupus erythematosus patients.

OBJECTIVE: To investigate the plasma galectin-3 levels in systemic lupus erythematosus (SLE) patients and its relations with clinical and laboratory features. METHODS: A total of 180 subjects with 90 patients with SLE (8 male, 82 female, mean age 37.86 ± 13.98 years) and 90 healthy controls (8 male, 82 female, mean age 36.54 ± 10.89 years) were included. Plasma galectin-3 levels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no significant difference in age and gender distribution between SLE patients and healthy controls (both P > .05). Plasma galectin-3 level was not significantly different between SLE patients and controls (P = .982) (P > .05). No significant difference was found regarding galectin-3 levels between SLE with nephritis and those without nephritis (P > .05); no significant difference was found between less active SLE and more active SLE (P > .05). Galectin-3 levels were inversely related to immune globulin M (r = -.303, P < .05), while no significant correlation between galectin-3 levels and other quantitative laboratory parameters were observed (all P > .05). CONCLUSIONS: In summary, plasma galectin-3 level was not significantly different between SLE patients and controls (P = .982). Further studies are needed to elucidate the role of galectin-3 in SLE.

Impact of the polymorphism in vitamin D receptor gene BsmI and the risk of systemic lupus erythematosus: an updated meta-analysis.

The etiology of system lupus erythematosus (SLE) still remains unclear, and vitamin D is associated with immune response. Although a few studies are conducted to investigate the association between polymorphism in vitamin D receptor (VDR) genes and SLE risk, their results are conflicting. Following the guideline of PRISMA, we conducted a systematic search and meta-analysis of the BsmI polymorphism rs1544410 and the risk of SLE. The pooled odds ratios (OR) and its 95 % confidential interval (CI) were calculated by using Stata Version 10 with dominant and recessive model and allele analyses. Nine studies were included in our meta-analysis with a total of 1247 SLE cases and 1687 controls. No significant association was found in both models in the overall population. Only Bb + BB genotypes showed a significantly elevated SLE risk in Asian subgroup with an OR of 3.26 (95 % CI = 1.30-8.17) while no significance was observed in Caucasian population. Notably, B allele significantly increased the SLE risk among Asian population with an OR of 2.29 (95 % CI = 1.14-4.61). No positive findings were reported in Caucasian population and in the overall analysis. In Asian population, Bb + BB genotype and B allele can significantly increase the SLE risk.