The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children

BackgroundType 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic β cells. PTPN22 and IL2RA polymorphisms have been found to be associated with several autoimmune diseases including T1D.AimsWe aimed to elucidate the role of PTPN22 and IL2RA polymorphisms in predisposition of T1D in Egyptian children.MethodsWe studied 150 children and adolescents with T1D and 165 healthy controls. The PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms were genotyped using polymerase chain reaction.ResultsWe found that carriers of the T allele of PTPN22 were significantly more likely to develop T1D (OR = 2.2, 95% CI = 1.2–4, P = 0.01). Also, the carrier of TT genotype and T allele of IL2RA more likely to develop T1D (OR = 2.8, 1.4, respectively, P = 0.03). There was a statistically significant association between T allele of PTPN22 gene and females ⩽10 years old at the onset of diabetes (OR = 4, 95% CI = 1.2–13.4, P = 0.019).ConclusionThis study suggests a possible association between the T allele of PTPN22 gene and TT genotype of IL2RA with T1D in studied Egyptian children, especially, females with early onset diabetes who carried the 1858T allele.     

CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians

ObjectiveLimited data are available on the genetics of rheumatoid arthritis (RA) in Egyptians. Therefore, we investigated whether the confirmed genetic risk factors for RA in Europeans and/or Asians contribute to RA susceptibility in Egyptians.Subjects and methodsA set of seven single-nucleotide polymorphisms (SNPs) in the vicinity of CD28, TNFAIP3, PTPN22, PADI4 and HLA-DRA were tested in a large multi-centric RA cohort in Egypt, consisting of 394 cases and 398 matched controls. Patients were stratified based on the positivity of either anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor (RF).ResultsSignificant association was evident for three SNPs in this cohort: the CD28 (rs1980422) variant showed a strong association in the whole cohort (P = 0.000119) and in seropositive subsets of the disease (P_ACPA+ = 0.004; P_RF+ = 0.0005). Upon stratification, the PTPN22 (rs2476601) and TNFAIP3(rs5029939) variants showed association only with ACPA positive (P_ACPA+ = 0.00573) and negative (P_ACPA− = 0.00999) phenotypes, respectively.ConclusionOur results suggest that CD28(rs1980422) and PTPN22(rs2476601) contribute to RA-susceptibility in Egyptians. Failure to replicate the association of PADI4(rs2240340)/(PADI4_94) in Egyptian RA patients provides further support for the notion that genetic architecture of RA is different in multiple populations of European, Asian, African, and Middle Eastern ancestries. Further investigation using large-scale studies is thus needed to maximize the power of genetic association.     

Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients

Objective

We investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn’s disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis.

Subjects

We analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants.

Methods

The analysis was carried out using PCR–RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls.

Results

We observed no significant difference of the examined variants between the patient and control groups.

Conclusions

Our results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Contribution of dendritic cell immunoreceptor (DCIR) polymorphisms in susceptibility of systemic lupus erythematosus and primary Sjogren’s syndrome

Dendritic cell immunoreceptor (DCIR) has previously shown an association with rheumatoid arthritis (RA) in Caucasians and Han Chinese. This study was aimed to further investigate whether DCIR polymorphisms are novel susceptibility factors for other autoimmune diseases, i.e. systemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (SS). A total of 1502 patients with SLE, 476 patients with primary SS, and 1278 non-related healthy controls were enrolled in the study. The single-nucleotide polymorphisms (SNPs) rs2377422 and rs10840759 were genotyped using TaqMan assay. The differences in allelic and genotypic distribution between two groups were assessed using Pearson chi-square test, and logistic regression adjusting for age and sex, respectively. P-value <0.025 was considered statistically significant by Bonferroni correction. The SNP rs2377422 confers an increased susceptibility risk to both SLE (allele model: P = 7.65 × 10⁻⁴, OR 1.20; genotype recessive model: P = 0.012, OR 1.29), and primary SS (allele model: P = 3.74 × 10⁻⁴, OR 1.31; genotype dominant model: P = 1.62 × 10⁻⁴, OR 2.02). There is no association between rs10840759 and SLE or primary SS. In conclusion, DCIR SNP rs2377422 is a novel genetic susceptibility factor for both SLE and primary SS.     

Association study of rs924080 and rs11209032 polymorphisms of IL23R-IL12RB2 in a Northern Chinese Han population with Behcet’s disease

ObjectivesTwo genome-wide association studies (GWAS) have identified the IL-23 receptor- IL-12 receptor β2 (IL23R-IL12RB2) as the susceptibility genetic region in Turkish and Japanese population with Behçet’s disease (BD). We investigated the association of this region with BD in a Northern Chinese Han population.MethodsA total of 407 patients with BD and 421 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) rs924080 and rs11209032 using the Sequenom MassArray system.ResultsStatistically significant associations with BD were detected at two SNPs namely, rs924080 and rs11209032, both, by allele analysis (OR = 1.58, 95% CI = 1.25–2.00, P_c = 2.52 × 10⁻⁴, and OR = 1.45, 95% CI = 1.19–1.76, P_c = 3.46 × 10⁻⁴, respectively), and genotype analysis (P_c = 1.22 × 10⁻³ and P_c = 1.77 × 10⁻³, respectively). Significant differences were observed in the genotype frequency distribution for these SNPs under the additive, dominant and recessive models (all P_c < 0.05). The haplotypes (AT and GC) formed by the two SNPs were associated with BD (all permutation P < 0.05). A meta-analysis also appeared to support the association of the two SNPs with BD.ConclusionSNPs (rs924080 and rs11209032) of the IL23R-IL12RB2 region were found to be associated with BD in a Northern Chinese Han population.     

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility

BackgroundMicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.MethodsA PubMed database search was conducted during August 2013 to identify case–control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.ResultsOur meta-analysis of six case–control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI = 0.642–1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR = 0.911, 95% CI = 0.710–1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR = 0.616, 95% CI = 0.384–0.981, (T vs. C allele) and OR = 0.386, 95% CI = 0.226–0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR = 1.263, 95% CI = 1.136–1.405, G vs. A allele).ConclusionsThe present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.     

Variants of the IL23R Gene are Associated with Ankylosing Spondylitis but not with Sjögren Syndrome in Hungarian Population Samples

Recently, associations were found between several autoimmune diseases and functional variants of interleukin-23 receptor (IL23R) gene; here, we studied the possible association of nine polymorphisms of IL23R with ankylosing spondylitis (AS) and with Sjögren syndrome (SS). In our study, we genotyped groups of patients with AS ( n  = 206), SS ( n  = 156) and healthy controls ( n  = 235) for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, rs11209026, rs10489629, rs7517847 and rs7530511 variants using PCR-RFLP methods. We observed significant increase in the carriage of the T allele of rs11805303 and the A allele of rs1004189 in the AS group compared with the controls. For the rs10889677 variant, the prevalence of the AA genotype and for the rs2201841, the CC genotype showed a more than two-fold increase in the AS group compared with the controls. By contrast, the GA heterozygous genotype of rs11209026 variant showed a significant decrease in AS patients compared with controls. Haplotype analysis revealed association of four IL23R haplotypes with AS. There was no difference in the distribution of any of the examined IL23R variants between controls and SS patients. In conclusion, we confirmed the susceptibility or protective associations of IL23R polymorphisms with AS in a Hungarian population and first demonstrated the involvement of the rs11805303 intronic single nucleotide polymorphisms, which was tested so far only for other autoimmune diseases.     

FCRL3 gene polymorphisms as risk factors for rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. As a member of FCRLs clusters, Fc receptor-like 3 (FCRL3) has been recognized as a neoteric autoimmune activation factor for RA. The aim of our study is to evaluate the correlation between four single-nucleotide polymorphisms (SNPs) on FCRL3 and RA risk in a Chinese Han population.Material and methodsThe hospital-based case-control study included 630 RA patients together with 696 healthy individuals as the control group and all subjects are Chinese ancestry. Four tagging single-nucleotide polymorphisms (tag-SNPs) on FCRL3 were selected and genotyped by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to evaluate the correlations between FCRL3 polymorphisms and RA. A systematic meta-analysis was also carried out based on the present study and previously published studies to further examine the association between FCRL3 variations and RA risk.ResultsSignificant association was found between −169T/C SNP and RA risk (CC vs. TT, OR = 1.62, 95% CI = 1.18–2.22; TC/CC vs. TT, OR = 1.47, 95% CI = 1.18–1.84; C vs. T, OR = 1.32, 95% CI = 1.12–1.54). Apart from that, mutations of −169T/C was significantly correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positive status. The meta-analysis also suggested that −169T/C mutation might have positive correlation with risk of RA in the overall population, particularly for Asian. Stratified analysis based on clinical characteristics of RF and ACPA also provided evidence that −169T/C polymorphisms could alter phenotypes of RA.ConclusionThe FCRL3 −169T/C variant was significantly linked with an increased RA risk in the Chinese Han population. Moreover, this meta-analysis also provides notion that −169T/C variant could act as a susceptible factor for RA. However, further investigations about the functional impacts of this polymorphism are essential to confirm the above conclusions.     

Effect of IL6 and IL23 on double negative T cells and anti ds-DNA in systemic lupus erythematosus patients

Several evidences suggest that DN T cells, IL23 and IL6 play a role in the pathogenesis of SLE. This study aimed to evaluate the frequency of DN T cells in SLE patients and the relation to their activity also to assess the possible role of IL6 and IL23 on DN T cells. Thirty patients with SLE and sixteen healthy blood donor females were enrolled. There was a significant increase in DN T cells in patients than controls (P = 0.001). These cells had a significant positive correlation with SLEDAI (r = 0.486, P = 0.006). DN T cells from SLE patient samples were expanded when stimulated in vitro with RhIL6 or RhIL23 in patients than controls. Furthermore, anti ds-DNA level was found to be increased in supernatant of PBMCs when stimulated by these cytokines in different concentrations. Our findings suggest that IL6 and IL23 may play role in SLE pathogenesis through their effect on DN T cells and anti ds-DNA.     

Investigation of association of the IL-12B and IL-23R genetic variations with psoriatic risk in a South Indian Tamil cohort

BackgroundPsoriasis is a T-cell mediated chronic systemic inflammatory skin disease. Emerging evidences suggest the interleukin (IL)-12B and IL-23R genes encoding the common p40 subunit of IL-12 and IL-23 are the key cytokines in T-helper (Th)1 and Th17 differentiation and function. Certain allelic variants of these genes significantly influence the risk of psoriasis. Hence we undertook to study the association of IL-12B and IL-23R gene polymorphisms with disease susceptibility in South Indian Tamil patients with psoriasis.Methods360 psoriatics and 360 healthy controls were included in this case control study. IL-12B gene (rs3212227) and IL-23R gene (rs2201841, rs10889677 and rs11805303) polymorphisms were typed by using TaqMan 5′allele discrimination assay and cytokine levels were assayed by ELISA.ResultsWe observed that the patients carrying the risk genotypes of IL-12B (rs3212227) and IL-23R (rs2201841) conferred an increased susceptibility to psoriasis. We did not find any significant association between IL-23R (rs10889677 and rs11805303) gene polymorphisms and psoriasis risk in South Indian Tamil population. We did not observe any significant difference in haplotypes between the psoriasis cases and controls. We observed a significant increase in the mean IL-23 levels in psoriatics and the higher levels of IL-23 were found in the minor variant genotype CC when compared with that of heterozygous CT and major variant TT genotypes of rs2201841. Individual genotypes of rs10889677 and rs11805303 and IL-12 (rs3212227) were not significantly associated with their plasma levels.ConclusionOur results suggest that IL-12B (rs3212227) and IL-23R (rs2201841) polymorphisms confer increased risk of psoriasis in our ethnic South Indian Tamils.     

Complex role of IL-23R polymorphisms on ankylosing spondylitis: a meta-analysis

Background: The aim of the meta-analysis was to evaluate the association between 10 widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and ankylosing spondylitis (AS).

Methods: A comprehensive literature search, screening of eligible articles and data extraction was performed independently by two investigators. Further meta-analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX, USA). The association between IL-23R polymorphisms and AS was evaluated by odds ratio (OR) and 95% confidence intervals (95% CI).

Results: Twenty-five case–control studies with 8431 cases and 8972 controls were included in this meta-analysis. Quantitative meta-analysis revealed that minor allele frequency (MAF) of rs1004819, rs1495965, and rs2201841 was significantly higher in the AS group (p value < .001, < .001, = .010, respectively). MAF of rs10489629, rs11209026, rs11465804, and rs1343151was significantly lower in the AS group (p value = .002, < .001, = .032, < .001, respectively). However, there is no significant difference between these two groups in rs10889677, rs11209032, and rs7517847 frequency (p value = .128, .237, .131, respectively).

Conclusions: The present study indicates that minor allele carriers of rs1004819, rs1495965, and rs2201841 are susceptible to AS. Conversely, minor alleles of rs10489629, rs11209026, rs11465804, and rs1343151 have protective effect on AS.     

Association of IL23R polymorphisms with psoriasis and psoriatic arthritis: a meta-analysis

Background

The association of variants in the IL23R gene with psoriasis and psoriatic arthritis (PsA) is a robust genetic finding

Objectives

To assess whether combined evidence shows the association between IL23R polymorphisms and susceptibility to psoriasis/PsA.

Methods

We conducted a meta-analysis to examine the association between the IL23R rs11209026 (Q381R), rs7530511 (L310P), and rs2201841 polymorphisms and psoriasis/PsA.

Results

Thirteen articles met the inclusion criteria and contributed data to the meta-analysis. For rs11209026, the odds ratios (ORs) of minor alleles for psoriasis and PsA were 0.616 [95?% confidence interval (CI) 0.563–0.674] and 0.630 (95?% CI 0.524–0.757), respectively. For rs7530511, the pooled ORs were 0.820 (95?% CI 0.764–0.879) for psoriasis and 0.875 (95?% CI 0.766–1.000) for PsA; for rs2201841 the OR was 1.121 (95?% CI 1.031–1.219) for psoriasis. In genotypic analysis, the association of rs11209026 (A) and rs7530511 (T) were compatible with the dominant model (P?P?=?0.001 respectively). The overall ORs for GG vs. AA (OR 1.339; 95?% CI 1.151–1.558), GG vs. GA (OR 1.143; 95?% CI 1.004–1.300), dominant (OR 1.226; 95?% CI 1.143–1.316), and recessive (OR 1.254; 95?% CI 1.115–1.411) models of rs2201841 were all significantly increased in psoriasis. No publication bias was present.

Conclusions

Our results demonstrate a significant association between IL23R gene polymorphisms and psoriasis/PsA.     

Association between KIR gene polymorphisms and rheumatoid arthritis susceptibility: A meta-analysis

ObjectivesThe results of studies on association between KIR (killer cell immunoglobulin-like receptors) polymorphisms and susceptibility to RA (rheumatoid arthritis) are inconsistent. To comprehensively evaluate the effect of KIR polymorphisms on the risk of RA, a meta-analysis was carried out.MethodsThe Web of Science, PubMed, the Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to select studies on the association between KIR polymorphisms and RA. The odds ratio (OR) with 95% confidence interval (95%CI) was obtained.ResultsNine qualified case–control studies were included in this meta-analysis. The results showed there were two positive associations of 2DL1, 2DS1 (OR_2DL1 = 2.20, 95%CI = 1.20–4.01, P_raw = 0.01, P_FDR = 0.03; OR_2DS1 = 1.84, 95%CI = 1.19–2.85, P_raw = 0.006, P_FDR = 0.018) and one negative association of 2DL3 (OR_2DL3 = 0.42, 95%CI = 0.22–0.79, P_raw = 0.006, P_FDR = 0.018) with susceptibility to RA in East Asians, but not in Caucasians.ConclusionThe current meta-analysis provides evidence that 2DL3 might be a potential protective factor and 2DL1, 2DS1 might be risk factors for RA in East Asians but not in Caucasians.     

Roles of ITPA and IL28B genotypes in chronic Hepatitis C patients treated with peginterferon plus ribavirin in Tunisian population

BackgroundDespite considerable progress in the treatment of chronic hepatitis C, many countries do not have access to these new treatments.ObjectivesPredictive markers of response to treatment are therefore necessary before initiating with historical combination therapy (PEG-IFN + ribavirin) for these populations.Study designWe therefore evaluated the influence of IL28B polymorphisms on treatment response and Inosine Triphosphate (ITPA) polymorphisms on the incidence of anaemia in a population of 120 Tunisian patients infected with HCV genotype 1b and treated.ResultsThe frequencies of favourable IL28B genotypes were 47% (CC for rs12979860) and 63% (TT for rs8099117). Patients in whom favourable IL28B alleles were identified had a higher chance of successful therapy: 82% for CC (rs12979860) and 75% for TT (rs8099117). Viral load decline during the first twelve weeks of treatment was more pronounced in patients with a favourable genotype (p < 0.0001). For patients with an unfavourable genotype, the second phase of viral decline was more pronounced in patients with SVR. A viral load decline cut-off of 2.68 log IU/mL at week 12 was best suited to discriminate responders from non-responders with an odds ratio of 40 (95% CI:11.53–170.3). Analysis of ITPA polymorphisms revealed that 16% of Tunisian patients presented ITPase deficiency. None of these patients experienced a decline of ribavirin doses during treatment versus 67% for patients without ITPase deficiency (p < 0.001).ConclusionThese data obtained in a Tunisian population should optimize before and during treatment the chances of success for treatments currently available in Tunisia for chronic HCV infection.     

IRF5, PTPN22, CD28, IL2RA,KIF5A,BLK and TNFAIP3 genes polymorphisms and lupus susceptibility in a cohort from the Egypt Delta; relation to other ethnic groups

ObjectiveTo replicate a single nucleotide polymorphism (SNP) of known genes for lupus (IRF5 rs10488631, PTPN22 rs2476601, BLK rs2736340 and TNFAIP3 rs5029939) and other autoimmune diseases (CD28 rs1980422, IL2RA rs2104286 and KIF5A rs1678542) on a newly studied Egyptian cohort to investigate the genetic disparity with different studied ethnic groups in relation to lupus susceptibility.Methods170 Egyptian patients from Egypt Delta with SLE and 241 matched healthy controls were genotyped by Taqman real time PCR for the selected SNPs.ResultsThe results revealed significant association with IRF5 (p < 0.0001) and PTPN22 (p = 0.008) and insignificant association with KIF5A, CD28, IL2RA, BLK and TNFAIP3 genes.ConclusionsThis study may provide an additional evidence for the association between IRF5 and PTPN22 and lupus susceptibility and may exclude it for CD28, IL2RA, and KIF5A.     

Epigenetic characteristics in inflammatory candidate genes in aggressive periodontitis

BackgroundPeriodontitis is a chronic inflammatory disease triggered by the host immune response. Epigenetic modifications also affect the immune response. We assessed CpG methylation in 22 inflammatory candidate genes (ATF2, CCL25, CXCL14, CXCL3, CXCL5, CXCL6, FADD, GATA3, IL10RA, IL12A, IL12B, IL13, IL13RA1, IL15, IL17C, IL17RA, IL4R, IL6R, IL6ST, IL7, INHA, and TYK2) with respect to the occurrence of aggressive periodontitis (AgP).Patients and methodsIn this study 15 AgP patients (53.3% males, 41.4 ± 10.5 years) and 10 controls (40.0% males, 36.9 ± 17.5 years) were included. The methylation patterns of gingival biopsies were quantified using EpiTect® Methyl Signature PCR Array Human Inflammatory Response.ResultsIn gingival biopsies taken from patients with AgP, CpG methylation of CCL25 (1.73% vs. 2.59%, p = 0.015) and IL17C (6.89% vs. 19.27%, p = 0.002) was significantly reduced as compared with periodontally healthy tissues.DiscussionWe showed for the first time a differential methylation pattern for CCL25 and IL17C in periodontitis. CCL25 plays an important role in T-cell development, whereas IL17C regulates innate epithelial immune responses. The decrease in CpG methylation is presumably accompanied by an increase in gene expression. This could lead to a greater availability of CCL25 and interleukin 17C and support periodontal loss of attachment.     

Serological markers of rheumatoid arthritis in patients with primary biliary cholangitis and the vice versa: A Tunisian study

BackgroundPrimary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destructive lymphocytic cholangitis and anti-mitochondrial antibodies (AMA). Anti-gp210 and anti-Sp100, are used for the diagnosis of PBC in AMA-negative PBC patients. Patients with PBC have a propensity to have an extrahepatic manifestation which is especially autoimmune.ObjectiveWe aimed to determine the frequency of serological markers of rheumatoid arthritis (RA) (CCP-Ab or RF) in PBC patients and to do the vice versa.MethodsOur PBC study included 70 patients with PBC and 80 healthy blood donors (HBD) and our RA study included 75 patients with RA and 75 HBD. Anti-cyclic citrullinated peptide antibodies (CCP-Ab) and rheumatoid factor (RF) were performed by indirect ELISA. AMA, anti-Sp100 and anti-gp210 were determined by indirect immunofluorescence.ResultsRA autoantibodies (CCP-Ab or RF) were more frequent in PBC patients than in HBD (65.7% vs. 8.7% p 〈1 0 ⁻⁶). CCP-Ab were significantly more frequent in patients than in controls (15.7% vs. 2.5%; p = 0.004). Nine patients had both CCP-Ab and RF vs. none of controls (12.8% vs. 0%; p = 0.001). RF were detected in 45 patients with PBC and in 5 HBD (64.3% vs. 6.2%; p 〈1 0 ⁻⁶). In PBC patients, RF were more frequent than CCP-Ab (64.3% vs. 15.7%; p 〈1 0 ⁻⁶). RF-IgG were present in 18.5% of patients; RF-immunoglobulin (Ig) A in 34.3% and RF-IgM in 54.3%. These frequencies were significantly higher than those found in control group (1.2% for RF-IgG (p 〈1 0 ⁻³); 0% for RF-IgA (p 〈1 0 ⁻⁶); and 6.2% for RF-IgM (p 〈1 0 ⁻⁶)). In our PBC patients, RF-IgA were more frequent than RF-IgG (34.3% vs. 18.5%; p = 0.03) and than CCP-Ab (34.3% vs. 15.7%; p = 0.01). Six patients had only RF-IgA versus none of the control group (8.6% vs. 0%; p = 0.01). AMA, anti-Sp100 and anti-gp 210 were absent in all RA patients.ConclusionsSerological markers of RA were more frequent in PBC patients than in HBD and the vice versa was not true.     

Tumor-associated antigens in systemic sclerosis and systemic lupus erythematosus: Associations with organ manifestations,immunolaboratory markers and disease activity indices

BackgroundSome tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected increased production of CA15-3, CA19-9 and CA125 in rheumatoid arthritis (RA). The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis.ObjectivesWe assessed levels of TAAs in the sera of SSc, SLE patients, patients with infectious diseases and healthy subjects. Serum TAA levels were correlated with each other, as well as with disease activity markers and organ involvement.MethodsTAAs including CEA, CA15-3, CA72-4, CA125 and CA19-9 were assessed by immunoassay in the sera of 92 patients with SSc, 40 patients with SLE, 50 age- and sex-matched healthy controls, as well as with 40 patients with current bacterial or viral infections. Normal upper limits for these TAAs were 3.4 mg/l, 25 kU/l, 6.9 kU/l, 35 kU/l and 34 kU/l, respectively.ResultsThere were significantly more SSc patients showing abnormally high levels of CA19-9 (8.8% vs 2.0%), CA125 (11.0% vs 6.0%) and CA15-3 (28.4% vs 14.0%) in comparison to controls (p < 0.05). In SLE, significantly more patients had elevated levels of CEA (32.5% vs 20.0%), CA19-9 (7.5% vs 2.0%), CA125 (15.0% vs 6.0%) and CA72-4 (15.0% vs 8.0%) than did controls (p < 0.05). The mean absolute serum levels of CEA (6.6 ± 1.7 vs 1.8 ± 1.4 mg/l) and CA15-3 (22.9 ± 1.8 vs 18.6 ± 2.2 kU/l) were also significantly higher in SSc compared to controls (p < 0.05). We found numerous correlations between the serum levels of different TAAs within the SSc and SLE population. Among SSc patients, serum CEA (R = 0.290; p = 0.005), CA15-3 (R = 0.260; p = 0.020) and CA19-9 (R = 0.257; p = 0.013) correlated with renal involvement. Serum CA15-3 also correlated with joint involvement (R = 0.329; p = 0.003), ANA positivity (R = 0.288; p = 0.010) and CRP levels (R = 0.407; p < 0.001). Within the SLE population, serum CA72-4 correlated with central nervous involvement (R = 0.624; p = 0.004) and CA125 correlated with the SLEDAI composite activity index (R = 0.666; p = 0.002). Patients with infections exerted serum TAA patterns similar to healthy controls.ConclusionThe concentration of some TAAs may be elevated in the sera of patients with SSc or SLE in comparison to healthy subjects. Pathogenically, most of these TAAs contain carbohydrate motifs and thus they may be involved in inflammation-associated adhesive events. Furthermore, the production of some TAAs may correlate with organ involvement or disease activity in scleroderma or lupus.