Aim
The aim of this case‐control study was to evaluate the association between the TNFSF13B rs9514828 (−871 C > T) polymorphism and soluble BAFF (sBAFF) in apical periodontitis (AP) patients.
...Methodology
Two hundred and sixty one healthy subjects (HS) and 158 patients with AP classified as: 46 acute apical abscess (AAA), 81 primary AP (pAP) and 31 secondary AP (sAP) patients were included. Genomic DNA (gDNA) was extracted from peripheral blood cells according to the salting out method. The TNFSF13B rs9514828 (NC_000013.11:g.108269025C > T) were identified using polymerase chain reaction (PCR) followed by restriction fragment length polymorphisms (RFLP). Serum sBAFF levels were measured by ELISA test. The chi‐squared or Fisher's exact test was performed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the risk of AP associated with the rs9514828. The Mann–Whitney U test and Kruskal–Wallis analysis were used for non‐normally distributed data. Differences were considered significant with a p‐value <.05.
Results
No differences in the genotype/allele frequencies were shown between HS and patients with AAA. However, the TT genotype (OR = 2.68, 95% CI: 1.10–6.53; p = .025) and T allele (OR = 1.46, 95% CI: 1.00–2.12; p = .045) were associated with increased risk of pAP. In contrast, the minor allele T significantly decreased the risk of sAP (OR = 0.49, 95% CI: 0.024–0.99; p = .043). sBAFF serum levels were increased in AAA and pAP compared with HS (p < .01 and p = .021, respectively). The AAA patients had higher sBAFF serum levels than pAP (p = .034) and sAP (p < .01).
Conclusions
These results suggest that the TNFSF13B rs9514828 (−871 C > T) polymorphism is associated with pAP susceptibility and that BAFF is a cytokine that might be involved in acute and chronic AP. The future exploration of the rs9514828 polymorphism in other AP cohorts is recommended.
Despite advances in understanding systemic lupus erythematosus (SLE), many challenges remain in unraveling the precise mechanisms behind the disease’s development and progression. Recent evidence has ...questioned the role of programmed cell death protein 1 (PD-1) in suppressing autoreactive CD4+ T cells during autoimmune responses. Research has investigated the potential impacts of PD-1 on various CD4+ T-cell subpopulations, including T follicular helper (Tfh) cells, circulating Tfh (cTfh) cells, and T peripheral helper (Tph) cells, all of which exhibit substantial PD-1 expression and are closely related to several autoimmune disorders, including SLE. This review highlights the complex role of PD-1 in autoimmunity and emphasizes the imperative for further research to elucidate its functions during autoreactive T-cell responses. Additionally, we address the potential of PD-1 and its ligands as possible therapeutic targets in SLE.
Introduction
B cell activating factor (BAFF) has an important role in normal B cell development. The aberrant expression of BAFF is related with the autoimmune diseases development like Systemic ...Lupus Erythematosus (SLE) for promoting self-reactive B cells survival. BAFF functions are exerted through its receptors BAFF-R (BR3), transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) that are reported to have differential expression on B cells in SLE. Recently, atypical B cells that express CD11c have been associated with SLE because they are prone to develop into antibody-secreting cells, however the relationship with BAFF remains unclear. This study aims to analyze the BAFF system expression on CXCR5
-
CD11c
+
atypical B cell subsets double negative 2 (DN2), activated naïve (aNAV), switched memory (SWM) and unswitched memory (USM) B cells.
Methods
Forty-five SLE patients and 15 healthy subjects (HS) were included. Flow cytometry was used to evaluate the expression of the receptors in the B cell subpopulations. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify the soluble levels of BAFF (sBAFF) and IL-21.
Results
We found increased frequency of CXCR5
-
CD11c
+
atypical B cell subpopulations DN2, aNAV, SWM and USM B cells in SLE patients compared to HS. SLE patients had increased expression of membrane BAFF (mBAFF) and BCMA receptor in classic B cell subsets (DN, NAV, SWM and USM). Also, the CXCR5
+
CD11c
-
DN1, resting naïve (rNAV), SWM and USM B cell subsets showed higher mBAFF expression in SLE. CXCR5
-
CD11c
+
atypical B cell subpopulations DN2, SWM and USM B cells showed strong correlations with the expression of BAFF receptors. The atypical B cells DN2 in SLE showed significant decreased expression of TACI, which correlated with higher IL-21 levels. Also, lower expression of TACI in atypical B cell DN2 was associated with high disease activity.
Discussion
These results suggest a participation of the BAFF system in CXCR5
-
CD11c
+
atypical B cell subsets in SLE patients. Decreased TACI expression on atypical B cells DN2 correlated with high disease activity in SLE patients supporting the immunoregulatory role of TACI in autoimmunity.
Background: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, which affects exocrine glands. T cell activation is a trigger mechanism in the immune response. Hyperreactivity of T ...cells and antibody production are features in pSS. ICOS can be critical in the pathogenesis of pSS. Methods: A total of 134 pSS patients and 134 control subjects (CS) were included. Genotyping was performed by PCR-RFLP. ICOS mRNA expression was quantified by real-time PCR, and CD4+ ICOS+ T cells were determined by flow cytometry. Results: The ICOS IVS1 + 173 T>C polymorphisms were not associated with susceptibility to pSS (p = 0.393, CI = 0.503−1.311). However, the c.1624 C>T polymorphism was associated with a reduction in the risk of development of pSS (p = 0.015, CI = 0.294−0.884). An increase in ICOS mRNA expression in patients was observed (3.7-fold). Furthermore, pSS patients showed an increase in membranal-ICOS expression (mICOS). High expression of mICOS (MFI) was associated with lymphocytic infiltration. Conclusions: The IVS1 + 173 polymorphism is not a genetic marker for the development of pSS, while c.1624 T allele was associated with a low risk. However, elevated mICOS expression in pSS patients with high lymphocytic infiltration was found. ICOS may have an important role in the immunopathogenesis of pSS and should be analyzed in T cell subsets in pSS patients as a possible disease marker.
Background
The increased expression of B cell‐activating factor (BAFF) has been linked to autoantibody production in autoimmune diseases (ADs). The aim of this study was to investigate the ...association among TNFSF13B gene (OMIM: 603969) single nucleotide polymorphisms (SNPs), TNFSF13B mRNA, and soluble BAFF (sBAFF) expression in patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). The diagnostic value of sBAFF also was evaluated by the area under the curve (AUC) of receiver operating characteristic or receptor (ROC) curves.
Methods
Genotypes of the TNFSF13B rs9514827 (−2841 T > C), rs1041569 (−2701 A > T) and rs9514828 (−871 C > T) SNPs were determined by PCR‐RFLP assay. TNFSF13B mRNA and sBAFF expression were performed by RT‐qPCR and ELISA, respectively. The study included 320 RA patients, 101 pSS patients, and 309 healthy subjects (HS).
Results
The rs9514828 T allele and the TAT haplotype were associated with an increased risk to develop RA. In both ADs, the TNFSF13B mRNA levels were increased in comparison with HS. The rs9514828 (−871 C > T) polymorphism was associated with increased gene expression in RA patients. Also, sBAFF levels were higher in both ADs, however pSS patients showed the highest sBAFF levels. sBAFF showed higher diagnostic performance for pSS with an AUC of 0.968, with a similar accuracy of anti‐SSA/Ro antibody diagnosis (AUC = 0.974).
Conclusions
Our findings demonstrate that the TNFSF13B rs9514828 (−871 C > T) polymorphism is a risk factor for RA in the western Mexican population. sBAFF levels may be a potential diagnosis biomarker in pSS.
TNFSF13B rs9514828 polymorphism is a risk factor for RA in western Mexican population. sBAFF levels are increased in RA and pSS patients. sBAFF showed higher diagnostic performance for pSS with AUC of 0.968, with similar accuracy of anti‐SSA/Ro antibody diagnosis.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with very heterogeneous clinical behavior between affected individuals. Therefore, the search for biomarkers clinically useful for ...the diagnosis, prognosis, and monitoring of the disease is necessary. Here, we determined the association between
,
,
, and
mRNA expression with the clinical characteristics and with the serum levels of IL-10, IFN-γ, and IL-17 in SLE patients. Forty patients with SLE and 34 control subjects (CS) were included, mRNA expression was determined by real-time qPCR and cytokine levels were quantified by a multiplex bead-based immunoassay. Compared to CS, SLE patients showed increased
mRNA and high IL-10 and IL-17 serum levels; in contrast,
mRNA and IFN-γ were decreased.
and
gene expression was negatively correlated with Mex-SLEDAI score and were notably downregulated in SLE patients with lupus nephritis. Interestingly, SLE patients with renal damage were the ones with the lowest levels of
and
mRNA and the highest SLEDAI scores. No associations were observed for
and
mRNA and IL-10, IL-17, and IFN-γ. In conclusion, we suggest that the assessment of
and
mRNA could be useful for monitoring disease activity in SLE patients showing renal involvement.
Background
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by destruction of exocrine glands as a result of T and B cells infiltrated in glandular tissue. CD28 and CTLA‐4 play ...a crucial role in T cell activation and inhibition. The aim of this study was to associate CD28 and CTLA4 haplotypes with susceptibility to pSS in patients from western Mexico.
Methods
Polymerase chain reaction and restriction fragment length polymorphism were performed to identify CD28 and CTLA4 genotypes in 111 patients with pSS and 138 control subjects (CS). Haplotype analysis was carried out by SHEsis program. Soluble serum levels of CD28 (sCD28) and CTLA‐4 (sCTLA‐4) were quantified by ELISA kit.
Results
The CD28 GC haplotype was associated with low risk to pSS (2.5‐folds, P < 0.001). CTLA4 CAG and CGA were identified as genetic risk factor (P < 0.001;OR = 3.82CI95%:2.022‐7.296 and P < 0.001; OR = 11.38CI95%:3.282‐37.69 respectively). No difference in sCD28 and sCTLA‐4 were found between patients and CS. However, pSS patients carriers of CD28 IVS3 + 17TC genotype showed high sCD28 (P = 0.039 vs TT carriers in CS). In regard to sCTLA‐4, patient who carry CTLA4‐319C>T, +49 A>G, and +6230 G>A, or their haplotypes did not show any difference.
Conclusion
Our findings suggest that CD28 GC, CTLA4 CAG, and CGA haplotypes are associated with susceptibility to pSS in patients from western Mexico. It seems that genetic control of CD28 and CTLA4 as well as local immune response in glandular tissue may regulate the impact of the gene expression in pSS. It is necessary to confirm this hypothesis in an integrative study.
B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play central roles in B cell development and maturation. Soluble forms of their receptors can be generated by proteolytic ...cleavage; however, their physiological and clinical roles are unknown. This study aimed to assess the relationships between the receptor soluble B cell maturation antigen (sBCMA) and clinical variables in systemic lupus erythematosus (SLE) patients. Serum cytokine concentrations were measured by ELISA for 129 SLE patients and 34 healthy controls (HCs), and the expression of the receptor BCMA was evaluated on B and plasma cells from 40 subjects. SLE patients showed aberrant expression of the receptor BCMA on B and plasma cells. Soluble levels of the receptor sBCMA and its ligands sAPRIL and sBAFF were increased in SLE patients compared with HCs. Additionally, sBCMA (r
= 0.6177) and sAPRIL (r
= 0.4952) correlated strongly with disease activity. Active SLE patients who achieved low disease activity showed decreased sBCMA (53.30 vs 35.30 ng/mL; p < 0.05) and sBAFF (4.48 vs 2.27 ng/mL; p < 0.05) serum levels after treatment, while sAPRIL expression remained unchanged. At a cutoff value of 22.40 ng/mL, sAPRIL showed high sensitivity (96.12%) and specificity (94.12%) for discrimination between HCs and SLE patients, while sBAFF showed lower sensitivity (82.2%) but higher specificity (94.1%) at a cutoff of 1.195 ng/mL. Relatively high levels of sAPRIL and sBCMA clustered active SLE patients. The receptor sBCMA could be a potential biomarker of disease activity in SLE.
Background: The B-cell activating factor (BAFF) controls the maturation and survival of B cells. An imbalance in this cytokine has been associated with systemic autoimmunity in SLE and lupus ...nephritis (LN). However, few investigations have evaluated the tissular expression of BAFF in LN. This study aimed to associate BAFF system expression at the tissular level with the proliferative LN classes. Methods: The analysis included eighteen kidney tissues, with sixteen LN (class III = 5, class IV = 6, class III/IV+V = 4, and class V = 1), and two controls. The tissular expression was evaluated with an immunochemistry assay. A Cytation5 imaging reader and ImageJ software were used to analyze the quantitative expression. A p-value < 0.05 was considered significant. Results: The expressions of BAFF, A proliferation-inducing ligand (APRIL), and their receptors were observed in glomerular, tubular, and interstitial zones, with BAFF being the most strongly expressed in the overall analysis. BAFF-Receptor (BR3), transmembrane activator and CALM interactor (TACI), and B-Cell maturation antigen (BCMA) displayed higher expressions in LN class IV in all zones analyzed (p < 0.05). Additionally, a positive correlation was found between APRIL, TACI, and BCMA at the glomerular level; BCMA and APRIL in the interstitial zone; and BR3, TACI, and BCMA in the tubule (p < 0.05). Conclusions: The expression of BAFF and BAFF receptors is mainly associated with LN class IV, emphasizing the participation of these receptors as an essential pathogenic factor in kidney involvement in SLE patients.
Background
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic ...clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups.
Methods
Ninety‐nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K‐mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal‐Wallis test and the Bonferroni test.
Results
Higher IFN‐γ, IL‐17F, IL‐21, IL‐23, IL‐4, and IL‐31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity.
Conclusion
Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.
Principal component analysis of 14 cytokines was realized to determine the cytokine groups in primary Sjögren´s syndrome patients. The mild group was characterized by less severity of the disease with low cytokine levels and fewer clinical parameters; the moderate group included patients with intermediate severity, presented higher cytokine levels than the mild group but less than severe group. Patients of the severe group showed higher severity, higher cytokine levels, and clinical parameters.
PDF
