Clinical and experimental rheumatology最新文献

Objectives: This study aimed to assess (1) effects of abatacept on salivary gland histology of Sjögren's disease (SjD) patients, (2) the predictive value of salivary gland histopathological characteristics at baseline for clinical response to abatacept treatment.

Methods: Patients (n=41) who participated in the Dutch ASAP-II and ASAP-III trials and international abatacept trial (IM101603) from whom a labial (n=13) or parotid (n=28) salivary gland biopsy was obtained at baseline and after 24 weeks of treatment with abatacept were included. Biopsies were analysed for SjD related histopathological features before and after abatacept (n=25) or placebo (n=16) treatment. Histopathological data at baseline were compared between clinical responders and non-responders to abatacept treatment.

Results: Comparison between abatacept- and placebo-treated patients revealed virtually no differences in histopathological parameters of parotid and labial salivary gland biopsies of SjD patients at baseline and 24 weeks after therapy. In labial glands, only the number of IgA plasma cells/mm2 differed between the two groups over time (p=0.034). Correspondingly in parotid glands, the number of IgA plasma cells increased in the abatacept group (p=0.049) after 24 weeks. The number of CD20+ B-cells/mm2 in parotid glands of the placebo group increased compared to baseline (p=0.021). There were no evident differences in baseline histopathological parameters between CRESS or ClinESSDAI responders and non-responders treated with abatacept.

Conclusions: Abatacept has limited effects on salivary gland histology in SjD patients after 24 weeks of treatment. Besides possibly affecting numbers of IgA plasma cells and preventing increases in B-lymphocyte infiltration, salivary gland histopathology could not predict response to abatacept treatment in SjD patients.

Objectives: Complicated primary Sjögren's syndrome (pSS) with haematological involvement (HI) is not uncommon; however, the aetiology of this condition remains obscure. The clinical characteristics, cytokine levels, and expression of peripheral blood lymphocyte subsets (CD4+ T lymphocyte subsets in particular) of patients with pSS-HI were investigated in this study.

Methods: The pSS-HI group (n = 43), the pSS complicated without HI (pSS-non-HI) group (n = 94), and the healthy controls (HCs) group (n = 40) were enrolled in the Second Hospital of Shanxi Medical University. The clinical data were gathered, and cytokines and peripheral blood lymphocyte subsets were quantified using flow cytometry and the Cytometric Bead Array (CBA), respectively.

Results: Patients with pSS-HI were more likely than those without pSS-HI to develop skin involvement, had a higher positive rate of anti-SSA antibody, and had elevated levels of IgA, IgG, and ESR. Compared to the pSS-non-HI group, the number of all lymphocyte subsets was lower in the pSS-HI group. However, the proportion of Th2 cells in the pSS-HI group was higher than those in the pSS-non-HI group. In contrast to the pSS-non-HI group, the pSS-HI group exhibited elevated levels of IL-10 and decreased levels of IL-4. A significant correlation was observed between IL-10 and the number of total T cells, CD4+ T cells, CD8+ T cells, NK cells, Th1 cells, Th2 cells, and Th17 cells. In the context of pSS-HI, protective factors may include the number of Treg cells and CD4+ T cells, whereas risk factors may include IgA and the number of Th2 cells.

Conclusions: An immunological mechanism potentially implicated in the development of pSS-HI may be the elevation of IL-10 and the reduction of peripheral blood CD4+ T cell subsets (particularly Treg cells) and serum IL-4 levels.

Objectives: In primary Sjögren's disease (pSjD), in addition to glandular inflammation and atrophy, functional secretion impairment may contribute to dryness. Altered protein distribution and antibodies against aquaporin-5 (anti-AQP5) and poly-U-binding factor 60kDa protein (anti-PUF60) have been reported in pSjD and may be specifically implicated in the glandular secretive processes. This study aimed to assess the occurrence of serum anti-AQP5 and anti-PUF60 antibodies and their correlations with clinical and laboratory features of pSjD.

Methods: Blood samples from pSjD patients and healthy donors (HD) were collected, and anti-AQP5 and anti-PUF60 antibodies were detected using an enzyme-linked immunosorbent assay. Differences between groups were evaluated using appropriate statistical tests, and odds ratios (OR) of high disease activity were assessed by multivariate stepwise backward multiple regression and adjusted for clinical covariates.

Results: Serum samples from 36 pSjD patients and 8 HD were analysed, and anti-AQP5 and anti-PUF60 antibody levels were not significantly different between groups. However, pSjD patients with high disease activity (n. 10) had significantly higher levels of anti-AQP5 antibodies compared to those with low-moderate disease activity (p<0.001). At logistic regression analysis, variables associated with high disease activity were anti-AQP5 (OR 128.9, 95% CI 2.7-615), C-reactive protein (OR 12.9, 95% CI 1.2-137.2), and C4 <10 mg/dl (OR 60, 95% CI 1.1-318.9).

Conclusions: Our pilot study confirms that anti-AQP5 antibodies may discriminate pSjD patients with high disease activity. These findings offer valuable clinical implications for managing pSjD patients, potentially identifying patients at high risk of glandular deterioration.

Objectives: To characterise the overlap syndrome between Sjögren's disease (SjD) and systemic lupus erythematosus (SLE).

Methods: Consecutive patients clinically defined as affected by SjD and SLE overlap syndrome (SjD-SLE), belonging to two Italian rheumatology centres were classified following the application of both the SjD and SLE classification criteria. Clinical, functional, ultrasound and histological data were compared with patients suffering from only SjD or SLE.

Results: Compared to SjD controls, SjD-SLE patients were younger at onset (p<0.0001). Schirmer's test and parotid swelling were comparable between the two groups, while unstimulated sialometry was more impaired in the SjD controls (p=0.0001). SjD-SLE cases showed increased joint (p=0.009), mucocutaneous (p<0.0001), renal (p=0.001) involvement, and serositis (p<0.0001). Ultrasound changes in the major salivary glands were prevalent in SjD controls, while the histological findings of the minor salivary glands were similar. Furthermore, SjD-SLE cases presented a higher prevalence of anti-SSA (p<0.0001) and lower presence of rheumatoid factor (p=0.008) and serum cryoglobulins (p=0.035). Compared to SLE controls, SjD-SLE were older (p=0.044). The frequency of extra-glandular manifestations of SjD-SLE was similar compared to SLE, including renal involvement. SjD-SLE patients showed higher prevalence of anti-SSA and anti-SSB (p<0.0001), C4 reduction (p=0.011), and leukopenia (p=0.025).

Conclusions: Our data further highlight the limitations of the application of the current classification criteria in overlap syndrome, since they are primarily based on clinical manifestations and common autoantibodies. Molecular signatures may explain clinical similarities and differences among systemic autoimmune diseases, and they may be particularly helpful in overlap syndromes.

Objectives: Focal lymphocytic sialadenitis (FLS) in minor salivary gland biopsy (MSGB) has long been regarded as a histologic hallmark of Sjögren's disease (SjD), but it can also occur in non-SjD individuals. This study aimed to define the prevalence of FLS in labial minor salivary glands of non-SjD individuals via both an autopsy study and a meta-analysis.

Methods: A total of 214 genotype-tissue expression (GTEx) volunteers was included in the autopsy study, and FLS in labial minor salivary gland was evaluated. A meta-analysis was also performed to comprehensively define the prevalence of FLS in labial minor salivary glands of non-SjD individuals.

Results: In the autopsy study of 214 GTEx volunteers, the frequency of FLS in labial minor salivary glands was 13.1%. GTEx volunteers aged 60 years and older demonstrated a greater prevalence of FLS compared to those volunteers younger than 60 years (20.3% vs. 9.7%, p=0.03). In the meta-analysis, a total of 8 eligible studies involving 917 labial minor salivary gland samples were included. The pooled prevalence of FLS in labial minor salivary glands of non-SjD individuals was 6.2%. In the subgroup analysis by gender, the pooled prevalence of FLS in labial minor salivary glands for female and male non-SjD individuals was 10.4% and 5.0%, respectively.

Conclusions: This study provides compelling epidemiological evidence for the considerably high prevalence of FLS in minor salivary glands of non-SjD individuals. The clinical significance of FLS should be cautiously considered when MSGB is used to confirm seronegative SjD.

Unlike other autoimmune diseases, little is known about the environmental risk factors for Sjögren's disease (SjD). Smoking is an important risk factor for rheumatoid arthritis but the relationship between smoking and SjD is more complex to understand. Current smoking seems to be negatively linked to SjD, whereas there is mixed data on past smoking. Smoking also seems to impact SjD outcomes, influencing comorbidities like hypertension or associated immune-mediated diseases, and, less clearly, extraglandular involvement, particularly pulmonary disease. Minor salivary gland biopsy findings indicate a lower frequency of positivity associated with smoking, with a potential dose-response relationship. However, smoking's uncertain effect on dryness symptoms complicates interpretation of data with reverse causation remaining a possibility. This review underscores the complexity of the smoking-SjD connection, raising questions about causality and potential protective effects on either SjD's development and/or classification criteria. Understanding these nuances may help unravel SjD pathogenesis and inform future therapeutic strategies.

Objectives: To assess work history, occupational exposure, smoking, and biomass fuel use in a Mexican IgG4-related disease (IgG4-RD) cohort.

Methods: We conducted a cross-sectional study among patients with IgG4-RD. A standardised questionnaire was used to collect data on occupational, smoking, and biomass fuel exposure. The International Standard Classification of Occupations (ISCO88) categorised patients into white-collar (ISCO88 groups 0-5) and blue-collar (ISCO88 groups 6-9) work.

Results: We included 95 patients, with a mean age of 53.8±15.8 years, and 50.5% were male. Seventy-eight (82.1%) had paid work: 63 (66.3%) in white-collar and 15 (15.8%) in blue-collar occupations. Of those who had no paid work, 13 (13.7%) did household work and 4 (4.2%) were students. White-collar jobs were more common than blue-collar jobs, both including (66.3% vs. 29.5%) and excluding (66.3% vs. 15.8%) unpaid household work. Pancreatobiliary involvement was not more frequent among blue-collar workers. Occupational exposure was reported by 31.6% of patients. White-collar workers had more lung involvement (29% vs. 7.1%, p=0.02) and less biomass exposure (19% vs. 64.3%, p<0.001). Occupational exposures were associated with the proliferative phenotype (OR 3.5, 95% CI 1.08-11.36). History of smoking was linked to increased lung involvement (OR 3.2, 95% CI 1.1-9.4), while biomass exposure was associated with the Mikulicz/systemic phenotype (OR 2.6, 95% CI 1.03-6.9).

Conclusions: This study shows that there are different patterns of occupational exposure among Mexican IgG4-RD patients, with fewer blue-collar jobs compared to other cohorts. Smoking and biomass fuel exposure may be more significant risk factors for IgG4-RD in this population, warranting further investigation.