The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sjögren's Syndrome.

Primary Sjögren's Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.

Clinical and Immunological Profile of Systemic Lupus Erythematosus: A 5-year Retrospective Analysis from Northeast India.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with a wide range of clinical manifestations having considerable variation in clinical features that are influenced by ethnic, sociocultural, and geographical factors. This disease primarily affects young women aged between 18 and 35 years. The aim of this present study was to delineate the clinical manifestations and immunological patterns of SLE patients from the Northeastern (NE) region of India. MATERIALS AND METHODS: The study was carried out in a tertiary care hospital from January 2016 to January 2021. Adult patients of age >18 years fulfilling systemic lupus international collaborating clinic criteria (SLICC) for classification of SLE were included in this study. Immunology such as antinuclear antibodies (ANA) and double-stranded deoxyribonucleic acid (dsDNA) were also performed followed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Over a period of 5 years, 142 patients were recruited for the study, with an overall female-to-male ratio was 9.9:1, a median age at onset of 25 years (interquartile range age 21-32 years) and a mean disease duration was 15.25 months (range 2-60 months). Our study revealed that ANA was positive in 97.18% of patients while anti-dsDNA was positive in 78.68%, indicating that women from this region have higher positivity rates. CONCLUSION: Our findings support the notion that SLE is a multisystem disorder that predominantly affects young females, especially during the second and third decades of life. Hematological, mucocutaneous, and renal manifestations are common in our patients. Moreover, pulmonary, cardiovascular, and gastrointestinal (GI) manifestations were understudied in other cohorts, which is one of our study's strengths.

Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan.

OBJECTIVE: To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE. METHODS: The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wide association study (GWAS) and PRS analyses of SLE and other three SLE markers, namely ANA, anti-double-stranded DNA antibody (dsDNA) and anti-Smith antibody (Sm), were conducted. RESULTS: Genetic variants associated with SLE were identified through GWAS. Some novel genes, which have been previously reported, such as RCC1L and EGLN3, were revealed to be associated with SLE in Taiwan. Multiple PRS models were established, and optimal cut-off points for each PRS were determined using the Youden Index. Combining the PRSs for SLE, ANA, dsDNA and Sm yielded an area under the curve of 0.64 for the optimal cut-off points. An analysis of human leucocyte antigen (HLA) haplotypes in SLE indicated that individuals with HLA-DQA1*01:01 and HLA-DQB1*05:01 were at a higher risk of being classified into the SLE group. CONCLUSIONS: The use of PRSs to predict SLE enables the identification of high-risk patients before abnormal laboratory data were obtained or symptoms were manifested. Our findings underscore the potential of using PRSs and GWAS in identifying SLE markers, offering promise for early diagnosis and prediction of SLE.

Frequency of sarcopenia in Turkish women with systemic lupus erythematosus.

OBJECTIVE: This study aimed to evaluate the prevalence of sarcopenia and its clinical significance in Turkish women with SLE, exploring the association between muscle mass, muscle strength and SLE disease activity. METHODS: A cross-sectional study was conducted at Gazi University Hospital's Department of Rheumatology from January to December 2020. It involved 82 patients with SLE, diagnosed according to the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria, and 69 healthy controls. Sarcopenia was assessed using hand grip dynamometry (hand grip strength (HGS)) and bioelectrical impedance analysis for muscle mass, with sarcopenia defined according to the 2018 European Working Group on Sarcopenia in Older People criteria and specific cut-offs for the Turkish population. The main outcomes measured were the presence of sarcopenia and probable sarcopenia, HGS values, skeletal muscle mass index and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: Among the patients with SLE, 51.2% met the criteria for probable sarcopenia and 12.9% were diagnosed with sarcopenia. The mean HGS was significantly lower in the SLE group (21.7±4.9 kg) compared with controls, indicating reduced muscle strength. The prevalence of anti-double-stranded DNA (anti-dsDNA) antibodies was 82.9%. Multivariate regression analysis identified height and levels of anti-dsDNA antibodies as independent predictors for developing probable sarcopenia. No significant association was found between clinical parameters, including SLEDAI-2K scores, and sarcopenia status. CONCLUSIONS: Sarcopenia is prevalent among Turkish women with SLE, with a significant proportion showing reduced muscle strength. The study found no direct association between sarcopenia and SLE disease activity or clinical parameters. These findings underscore the importance of including muscle strength assessments in the routine clinical evaluation of patients with SLE to potentially improve management and quality of life.

Clinical features of patients with systemic sclerosis positive for anti-SS-A antibody: a cohort study of 156 patients.

BACKGROUND: Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren's syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc. METHODS: A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis. RESULTS: This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14-6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99-4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23-32.60; P = 0.024). CONCLUSIONS: Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.

Association between serum antinuclear antibody and rheumatoid arthritis.

Background: The relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case-control study. Methods: Patients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis. Results: A total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively. Conclusion: There was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.

Seronegative patients with primary Sjögren's syndrome and non-pSS sicca test positive for anti-SSA/Ro52 and -Ro60 in saliva.

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.

The Expression Levels of TREX1 and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals.

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.

Antinuclear antibody titration and pattern are helpful in the diagnosis of systemic autoimmune rheumatic diseases.

INTRODUCTION: Anti-nuclear antibody (ANA) testing is among the most common immunological test requested in the diagnostic immunology laboratory. The main purpose of this test is to screen for the underlying systemic autoimmune rheumatic diseases (SARDs). The gold standard laboratory method for ANA detection is by the indirect immunofluorescence (IIF) assay. In most laboratories, positive ANA-IIF is reported in terms of titration and pattern. OBJECTIVE: This study was conducted with the aim of determining the correlation between ANA-IIF titration and pattern for the diagnosis of SARDs. MATERIALS AND METHODS: A retrospective study was conducted whereby the positive ANA-IIF samples from 1st July 2018 until 31st December 2019 and 1st January 2021 until 31st March 2021 were included in this study. The duplicate samples were excluded. ANA-IIF titration and pattern were recorded for all patients. The demographic, clinical, and final diagnosis data were retrieved from each patient's clinical note. RESULTS: A total of 179 patients were included for analysis. The majority of the patients were female (79.9%) and from Malay ethnicity (66.5%). Sixty-five patients (36.3%) had ANA-IIF positive at 1:80 titration followed by 45 patients (25.1%) positive at titration of equal or more than 1:160. Speckled was the predominant pattern visualised in 90 patients (50.3%) followed by homogeneous in 76 patients (42.5%). Forty-five patients (25.1%) were finally diagnosed with SARDs with 41 of them diagnosed as SLE. ANA titration was significantly associated with the final diagnosis of SARDs at all titres (p<0.001) but the best cut-off was noted at a titre of equal or more than 1:320 with the sensitivity and specificity of 86.7% and 77.6% respectively. The homogeneous pattern was also significantly associated with SARDs (p=0.04). The final diagnosis of SARDs were significantly higher in female (p=0.03) and their age was significantly younger (p<0.001). CONCLUSION: ANA-IIF titration of equal or more than 1:320 can be used as the best titration for differentiating between SARDs and non-SARDs in a positive ANA sample. Patients with homogeneous pattern were more likely to be diagnosed with SARDs than other ANA-IIF patterns.

Methyl-supplemented nutrition delays the development of autoimmune disease in pristane-induced murine lupus.

The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl-supplemented nutrition on the development of SLE was studied in the pristane-induced mouse model of the disease. The results clearly demonstrated decreased anti-dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed. The beneficial effect of the diet is due to the methyl-containing micronutrients with possible anti-inflammatory and immunomodulating effects on cell proliferation and gene expression. Since these components are responsible for maintaining the physiological methylation level of DNA, the results point to the central role of methylation processes in environmentally triggered lupus. As nutrition represents one of the major epigenetic factors, these micronutrients may be considered novel agents with significant therapeutic outcomes.

Major low-energy trauma results in non-specific immunoglobulin generation without evidence for specific autoantibody production: A prospective cohort study.

Cellular debris resulting from large trauma might overwhelm the scavenger mechanisms and lead to autoimmune reactions. We analysed whether a major well-defined trauma in humans induces laboratory signs of transient autoimmunity in the months after the insult. We included 50 patients with pertrochanteric femur fracture undergoing intramedullary nail osteosynthesis in a prospective cohort study and followed them at 3-4 days, 6 weeks, 12 weeks and 12 months postoperatively. By standard techniques, we assessed levels of total immunoglobulins, anti-nuclear antibodies (ANA), anti-cardiolipin antibodies, anti-dsDNA antibodies and anti-C1q antibodies, as well as antibodies against cytomegalovirus (CMV) as a control. Blood leukocyte differential and lymphocyte subpopulations were determined at baseline and in the first two postoperative samples. The mean age of the patients reached 80.1 years, and 23 (46%) completed all visits. Serum concentrations of total IgG, IgM and IgA increased at all follow-up time points. The ANA fluorescence light intensity units increased at 12 weeks and 12 months postoperatively (p < 0.0001), but the proportion of ANA-positive patients did not change (35%). The values of anti-C1q mildly increased at all follow-up visits, but not the ratio to total IgG. Anti-dsDNA remained negative in all patients, and anti-cardiolipin IgG/IgM antibodies did not change. Anti-CMV IgG antibodies increased significantly at all follow-up visits, without change in the ratio to total IgG. Flow cytometry showed an increased proportion of B-cells 3-4 days postoperatively. In conclusion, major musculoskeletal trauma in elderly patients induces a generalized non-specific increase in immunoglobulin production without laboratory signs for enhanced systemic autoimmunity.

A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence.

Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.

Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis.

OBJECTIVES: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort. METHODS: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719). FINDINGS: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]). INTERPRETATION: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.

Comparison of patients with isolated cutaneous lupus erythematosus versus systemic lupus erythematosus with cutaneous lupus erythematosus as the sole clinical feature: A monocentric study of 149 patients.

BACKGROUND: Cutaneous lupus erythematosus (CLE) may present as an isolated entity or be classified as Systemic lupus erythematosus (SLE) by the presence of laboratory abnormalities, including cytopenia, low complement levels, and/or autoantibodies (CLE with laboratory SLE). OBJECTIVE: To compare isolated CLE and CLE with laboratory SLE and to validate an existing 3-item score with age < 25 years (1 point), phototypes V to VI (1 point), antinuclear antibodies ≥ 1:320 (5 points) to predict the risk of progression from CLE to severe SLE (sSLE). METHODS: Monocentric cohort study including consecutive patients with CLE. CLE with laboratory SLE was defined by 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE score of ≥10 points at baseline with CLE as the sole clinical feature. RESULTS: Of the 149 patients with CLE, 20 had CLE with laboratory SLE. The median follow-up duration was 11.3 years (IQR: 5.1-20.5). Ten patients (7%) had sSLE developed. In survival analysis, the risk of progression to sSLE was higher among CLE with laboratory SLE (hazard ratio = 6.69; 95% CI: 1.93-23.14, P < .001) compared to isolated CLE. In both groups, none of the patients with a risk score ≤ 2 had sSLE developed. LIMITATIONS: Monocentric study with a limited number of patients. CONCLUSIONS: CLE with laboratory patients with SLE have a higher risk of progression to sSLE than isolated CLE.

Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Serum IgE anti-dsDNA autoantibodies in patients with proliferative lupus nephritis are associated with tubulointerstitial inflammation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overproduction of multiple autoantibodies. Lupus nephritis (LN), the most common cause of morbidity and mortality, requires early detection. However, only a limited number of serum biomarkers have been associated with the disease activity of LN. Serum IgE anti-dsDNA autoantibodies are prevalent in patients with SLE and may be associated with the pathogenesis of LN. In this study, serum samples from 88 patients with biopsy-proven proliferative LN were collected along with complete clinical and pathological data to investigate the clinical and pathological associations of anti-dsDNA IgE autoantibodies using ELISA. This study found that the prevalence of IgE anti-dsDNA autoantibodies in patients with proliferative LN was 38.6% (34/88). Patients with anti-dsDNA IgE autoantibodies were more prone to acute kidney injury (17/34 vs. 14/54; p = .025). Levels of anti-dsDNA IgE autoantibodies were associated with interstitial inflammation (r = 0.962, p = .017). Therefore, anti-dsDNA IgE autoantibody levels are associated with tubulointerstitial inflammation in patients with proliferative LN.

Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus.

The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value.

Asociaciones de hallazgos diagnósticos con actividad de la enfermedad en el síndrome de Sjogren primario: un análisis de conglomerados / Associations of diagnostic findings with disease activity in primary Sjogren's syndrome: a cluster analysis

Objective The diagnosis of primary Sjӧgren's syndrome still relies upon a constellation of clinical, laboratory, imaging, and pathological findings. We aimed to evaluate the relation of the disease activity with the results of diagnostic tests for primary Sjӧgren's syndrome. Methods A principal component with cluster analysis was performed to classify 69 patients with primary Sjӧgren's syndrome based on the results of diagnostic evaluations. Results Anti-SSA autoantibody was the most represented feature on the principal components. The anti-SSA and ultrasound score were positively correlated (p=0.001). We identified two distinct clusters of low or high disease activity (p<0.001). Except for disease duration and serum beta2-microglobulin, the clusters were significantly different in salivary flow (p= 0.004), ultrasound findings (p<0.001), IgG (p= 0.001), and salivary beta2-microglobulin (p= 0.048). Also, positive findings were significantly different between the clusters in rheumatoid factor, antinuclear antibody, anti-SSA, and anti-SSB (all p≤0.013). Conclusion Patients with higher syndrome activity were best recognized with serological and ultrasound assessments. However, patients with lower syndrome activity had a longer disease duration, higher stimulated salivary flow rate, and a positive biopsy of minor salivary glands (56%) (AU)

Objetivo El diagnóstico del síndrome de Sjӧgren primario todavía se basa en una constelación de hallazgos clínicos, de laboratorio, de imagen y patológicos. Nuestro objetivo fue evaluar la relación de la actividad de la enfermedad con los resultados de las pruebas diagnósticas para el síndrome de Sjӧgren primario. Métodos Se realizó un análisis de componentes principales mediante conglomerados para clasificar a 69 pacientes con síndrome de Sjӧgren primario en función de los resultados de las evaluaciones de diagnóstico. Resultados El autoanticuerpo anti-SSA fue la característica más representada en los componentes principales. El anti-SSA y la puntuación de ultrasonido se correlacionaron positivamente (p=0,001). Identificamos dos grupos distintos de baja o alta actividad de la enfermedad (p<0,001). Excepto por la duración de la enfermedad y la microglobulina beta2 sérica, los grupos fueron significativamente diferentes en el flujo salival (p=0,004), los hallazgos de ultrasonido (p<0,001), IgG (p=0,001) y microglobulina beta2 salival (p=0,048). Además, los hallazgos positivos fueron significativamente diferentes entre los grupos en factor reumatoide, anticuerpo antinuclear, anti-SSA y anti-SSB (todos p≤0,013). Conclusión Los pacientes con mayor actividad del síndrome se reconocieron mejor con evaluaciones serológicas y ecográficas. Sin embargo, los pacientes con menor actividad del síndrome tenían una mayor duración de la enfermedad, mayor tasa de flujo salival estimulado y una biopsia productiva de glándulas salivales menores (56%) (AU)

Immune-mediated necrotizing myopathy (NAM) related to SARS-Cov-2 infection: a case report.

BACKGROUND: There is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies. CASE PRESENTATION: We described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline. CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

Serum cytokines to predict systemic lupus erythematosus clinical and serological activity.

We aimed to explore the role of interleukin (IL)-6, interferon-gamma (IFNγ), IL-10, and tumor necrosis factor (TNF) as predictors of systemic lupus erythematosus (SLE) clinical and serological activity, and their correlation with the treatment received. We performed a retrospective analysis of 77 patients with SLE according to the 2012 Systemic Lupus International Collaborative Clinics (SLICC) criteria. The outcomes were serological activity (SA), active disease (AD), complete remission (CR), the low-disease activity state (LDAS), and immunosuppressive treatment. SA was present in 17.1%, AD in 17.3%, CR in 13%, and LDAS in 64.9% of patients. IL-6 values were higher in patients in SA, in AD, in those receiving steroids alone, and in patients without CR or LDAS (p < 0.05). IFNγ was associated with anti-double stranded DNA (dsDNA) antibodies positivity and immunosuppression, whereas IL-10 values were higher in patients with CR (p < 0.05). The IL6-IFN product was able to predict anti-double stranded DNA (anti-dsDNA) antibodies positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.705, 95% confidence interval [CI] 0.563-0.847), SA (AUC-ROC = 0.720, 95% CI 0.542-0.899), AD (AUC-ROC = 0.701, 95% CI 0.520-0.882), steroid treatment (AUC-ROC = 0.751, 95% CI 0.622-0.879), and the absence of LDAS (AUC-ROC = 0.700, 95% CI 0.558-0.834). The IL6-IFN/IL10 ratio predicted AD (AUC-ROC = 0.742, 955 CI 0.540-0.944), steroid treatment (AUC-ROC = 0.721, 95% CI 0.572-0.870), and the absence of LDAS (AUC-ROC = 0.694, 95% CI 0.536-0.853). In conclusion, IL-6, IL-10, and IFNγ might help to assess SLE serological and clinical activity. Their combination in the IL-6-IFN product and the IL-6xIFN to IL-10 ratio results in novel tools to determine and predict SA, AD, and LDAS. Prompt detection of SLE activity might allow a rapid intervention to avoid established or chronic damage.