Anti-citrullinated protein antibodies and arthritis in Sjögren's syndrome: a systematic review and meta-analysis.

OBJECTIVE: The presence of anti-citrullinated protein antibodies (ACPAs) in primary Sjögren's syndrome (pSS) ranges from 3% to 9.9%; however, there is no agreement about their clinical significance. Our aim was to systematically review the literature regarding the association of arthritis and ACPAs in pSS and their role in the development of rheumatoid arthritis (RA). METHOD: A comprehensive search of MEDLINE, ISI Web of Knowledge, and Cochrane Library from inception until June 2016 was undertaken using the combination of two or three of the keywords: primary Sjögren's syndrome, Sjögren's syndrome, arthritis, synovitis, arthropathy, anti-cyclic citrullinated peptide antibodies, and anti-citrullinated protein antibody - ACPA. No language restriction was used. Studies were included if they: assessed the association of arthritis and ACPAs, had sufficient data to construct a two-by-two table, tested immunoglobulin G ACPA by any method, and included patients with pSS according to a validated set of classification criteria. We used a random effects model and evaluated the heterogeneity and publication bias. RESULTS: Ten studies were included (involving 1322 patients). We found a pooled odds ratio of 4.42 (95% confidence interval 1.15-16.94, p = 0.03). The test for heterogeneity was I2 = 0.87. Publication bias was not observed. Based on data from three studies, 33 of 58 pSS patients with ACPAs (57%) developed RA compared with none of 598 pSS patients with negative ACPA (p < 0.000001). CONCLUSION: Patients with pSS disclosing ACPAs are prone to arthritis as part of the clinical spectrum of the disease, but are also at risk of developing RA.

Clinical and nerve conduction features in Guillain-Barré syndrome associated with Zika virus infection in Cúcuta, Colombia.

BACKGROUND AND PURPOSE: Zika virus (ZIKV) infection has been associated with an increased incidence of Guillain-Barré syndrome (GBS) but the relative frequency of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and axonal GBS subtypes is controversial. METHODS: Twenty GBS patients diagnosed according to the Brighton criteria during the ZIKV outbreak in Cúcuta, Colombia, were evaluated clinically and electrophysiologically. The electrodiagnosis of GBS subtypes was made according to a recently described criteria set that demonstrated a high diagnostic accuracy on the basis of a single test. The electrophysiological features of 34 Italian AIDP patients were used as control. RESULTS: All patients had symptoms compatible with ZIKV infection before the onset of GBS and ZIKV infection was laboratory confirmed through a plaque reduction neutralization test (PRNT90 ) in 100% of patients. The median time from onset of ZIKV infection symptoms to GBS was 5 days (interquartile range 1-6 days). Cranial nerve palsy was present in 85% of patients (facial palsy in 75%, bulbar nerve involvement in 60%), autonomic dysfunction in 85%, and 50% of patients required invasive mechanical ventilation. AIDP was diagnosed in 70% of patients. 40% of nerves of AIDP patients showed a prevalent distal demyelinating involvement but this pattern was not different from the Italian AIDP patients without ZIKV infection. CONCLUSIONS: Guillain-Barré syndrome associated with ZIKV infection in Cúcuta is characterized by a high frequency of cranial nerve involvement, autonomic dysfunction and requirement of mechanical ventilation indicating an aggressive and severe course. AIDP is the most frequent electrophysiological subtype. Demyelination is prevalent distally but this pattern is not specific for ZIKV infection.

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study.

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

The autoimmune tautology with a focus on antiphospholipid syndrome.

Autoimmune diseases (ADs) are often diagnosed according to classification criteria; however, they share similar subphenotypes including signs and symptoms, non-specific autoantibodies and other immune changes, which are prone to taxonomic problems. Polyautoimmunity is defined as the presence of more than one AD in a single patient. The close relationship between antiphospholipid syndrome (APS) and systemic lupus erythematosus has been studied throughout the years. However, APS may coexist with several other ADs confirming polyautoimmunity in this systemic disease. Herein, we summarized the common characteristics shared between APS and others ADs in light of the autoimmune tautology (that is, common mechanisms of autoimmune diseases).

Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations characterized by the development of pathogenic autoantibodies manifesting in inflammation of target organs such as the kidneys, skin and joints. Genome-wide association studies have identified genetic variants in the UBE2L3 region that are associated with SLE in subjects of European and Asian ancestry. UBE2L3 encodes an ubiquitin-conjugating enzyme, UBCH7, involved in cell proliferation and immune function. In this study, we sought to further characterize the genetic association in the region of UBE2L3 and use molecular methods to determine the functional effect of the risk haplotype. We identified significant associations between variants in the region of UBE2L3 and SLE in individuals of European and Asian ancestry that exceeded a Bonferroni-corrected threshold (P<1 × 10(-4)). A single risk haplotype was observed in all associated populations. Individuals harboring the risk haplotype display a significant increase in both UBE2L3 mRNA expression (P=0.0004) and UBCH7 protein expression (P=0.0068). The results suggest that variants carried on the SLE-associated UBE2L3 risk haplotype influence autoimmunity by modulating UBCH7 expression.

Concordance of CCR5 genotypes that influence cell-mediated immunity and HIV-1 disease progression rates.

We used cutaneous delayed-type hypersensitivity responses, a powerful in vivo measure of cell-mediated immunity, to evaluate the relationships among cell-mediated immunity, AIDS, and polymorphisms in CCR5, the HIV-1 coreceptor. There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression. In the cohorts examined, CCR5 genotypes containing -2459G/G (HHA/HHA, HHA/HHC, HHC/HHC) or -2459A/A (HHE/HHE) associated with salutary or detrimental delayed-type hypersensitivity and AIDS phenotypes, respectively. Accordingly, the CCR5-Δ32 allele, when paired with non-Δ32-bearing haplotypes that correlate with low (HHA, HHC) versus high (HHE) CCR5 transcriptional activity, associates with disease retardation or acceleration, respectively. Thus, the associations of CCR5-Δ32 heterozygosity partly reflect the effect of the non-▵32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayed-type hypersensitivity with -2459G/G-containing CCR5 genotypes, reduced CCR5 expression, decreased viral replication, and disease retardation suggest that CCR5 may influence HIV infection and AIDS, at least in part, through effects on cell-mediated immunity.

Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P=2.99E-13, OR=5.2, 95% CI=3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis.

Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases.

Copy number variation (CNV) in the human genome is an important determinant of susceptibility to autoimmune diseases. Many autoimmune diseases share similar clinical and pathogenic features. Thus, CNVs of genes involved in immunity may serve as shared determinants of multiple autoimmune diseases. Here, we determined the association between CNV in the gene encoding FCGR3B with the risk of developing autoimmune diseases and whether the observed associations are modified by the CNV in CCL3L1 (CC chemokine ligand 3-like 1), a gene encoding a potent chemokine. In a cross-sectional study of 774 subjects, we estimated FCGR3B and CCL3L1 gene copy number in 146, 158 and 61 subjects with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS), respectively, and 409 healthy controls. The median gene dose of FCGR3B in the study population was two. FCGR3B copy number < or >2 was associated with an increased risk of SLE and primary SS but not RA. This association was mostly evident in subjects who also had two copies of CCL3L1. Thus, our data suggest that epistatic interactions between CNV of FCGR3B and CCL3L1, two immune response genes, may influence phenotypically related autoimmune diseases.

Bcl-2 antagonist killer 1 (BAK1) polymorphisms influence the risk of developing autoimmune rheumatic diseases in women.

OBJECTIVE: Bcl-2 antagonist killer 1 (BAK1) is a Bcl-2 family proapoptotic member suggested as a candidate gene for autoimmune diseases. The influence of BAK1 polymorphisms on the risk of developing autoimmune rheumatic diseases (AIRDs) in women was investigated. METHODS: A total of 719 Colombian women were included in the present study: 209 had systemic lupus erythematosus, 99 primary Sjögren syndrome, 159 rheumatoid arthritis and 252 were healthy matched controls. Tag single nucleotide polymorphisms (SNPs) and potentially functional variants were typed by TaqMan allele discrimination assays. HLA-DRB1 and HLA-DQB1 typing was performed by reverse dot-blot hybridisation and linkage disequilibrium (LD) with BAK1 SNPs was assessed. RESULTS: SNPs rs513349 (odds ratio (OR) 0.57, 95% CI 0.46 to 0.72, p = <0.001) and rs5745582 (OR 1.61, 95% CI 1.26 to 2.04, p = <0.001) were associated with the AIRDs included in this study. There was a significant increase of the rs513349G-rs561276C-rs5745582A (GCA) haplotype in each patient cohort as compared to controls (OR 1.95, 95% CI 1.50 to 2.54, p = <0.001). These SNPs were not in LD with HLA-DRB1 or HLA-DQB1 genes. CONCLUSIONS: The results indicate that the BAK1 polymorphisms influence the risk of acquiring AIRDs in the population studied and are consistent with the paradigm that autoimmune diseases are likely to share common susceptibility variants.

Infectious antibodies in systemic lupus erythematosus patients.

Infections can act as environmental triggers that induce or promote systemic lupus erythematosus (SLE) in genetically predisposed individuals. New technologies, developed recently, enable simultaneous assessment of multiple antibodies. Antibodies to specific infectious agents may shed light into the mechanisms of induction of SLE. The aim of this study was to investigate the prevalence of seropositivity and the titers of antibodies to bacterial, viral, and parasitic agents in SLE patients compared with non-autoimmune controls. Sera from 260 individuals (120 SLE patients and 140 controls) were tested by the BioPlex 2200 Multiplexed Immunoassay method (BioRad) for the prevalence and titers of antibodies to eight infectious agents (Epstein-Barr virus: early antigen IgG, nuclear antigen IgG, viral capsid antigen IgG and IgM, heterophile IgM; cytomegalovirus IgG and IgM; Toxoplasma gondii IgG and IgM; rubella IgG and IgM; Treponema pallidum TPr15G, TPr17G, TPr47G; herpes simplex virus type 1 and 2 IgG; hepatitis C virus and hepatitis B core antibodies. Cytomegalovirus IgM and Epstein-Barr virus early antigen IgG (but not other Epstein-Barr virus antigens) were significantly more prevalent in SLE patients than in controls. Conversely, positive titers of hepatitis B core and rubella IgG antibodies were less prevalent in the SLE patients than in controls. Other differences in titer positivity prevalence were not detected between patients and controls. The titers of the cytomegalovirus IgM, Toxoplasma IgG, Epstein-Barr virus early antigen, and viral capsid antigen IgG antibodies were significantly higher in SLE compared with controls. Our data suggest the importance of previous exposure to infectious agents in the induction and the prevention of SLE.

Characterization of Implanted Stents through Neointimal Tissue Bioimpedance Simulations.

This work describes how is possible the definition of the light hole or lumen in implanted stents affected by restenosis processes using the BioImpedance (BI) as biomarker. The main approach is based on the fact that neointimal tissues implied in restenosis can be detected and measured thanks to their respective conductivity and dielectric properties. For this goal, it is proposed a four-electrode setup for bioimpedance measurement. The influence of the several involved tissues in restenosis: fat, muscle, fiber, endothelium and blood, have been studied at several frequencies, validating the setup and illustrating the sensitivity of each one. Finally, a real example using a standard stent, has been analyzed for stable and vulnerable plaques in restenosis test cases, demonstrating that the proposed method is useful for the stent obstruction test. Bioimpedance simulation test has been performed using the electric physics module in COMSOL Multiphysics®.

STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians.

The aim of this study was to determine the influence of STAT4 (rs7574865) and TRAF1/C5 (rs10818488 and rs2900180) gene polymorphisms on the risk of developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Colombian population. This was a case-control study in which 839 individuals with RA (N=274) and SLE (N=144) and matched healthy controls (N=421) were included. Genotyping was performed by using a polymerase chain reaction system with pre-developed TaqMan allelic discrimination assay. STAT4 rs7574865T allele disclosed a significant influence on the risk of developing SLE (P=0.0005; OR 1.62, 95% CI 1.22-2.16) and RA (P=0.008; OR 1.36; 95% CI 1.08-1.71), whereas no effect on these autoimmune diseases was observed for the TRAF1/C5 polymorphisms examined. Our data strengthen STAT4 rs7574865 polymorphism as a susceptibility factor for RA and SLE and provide further evidence for a common origin of autoimmune diseases.

CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus.

OBJECTIVES: There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1-gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE. METHODS: We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5. RESULTS: Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-Delta32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual's CCL3L1-CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential recruitment of leukocytes in subjects with lupus nephritis. The CCR5 HHE/HHG*2 genotype was associated with the maximal risk of developing SLE. CONCLUSION: CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1-CCR5 axis in the pathogenesis of SLE.

Delayed lupus nephritis.

OBJECTIVE: To describe and analyse the clinical and immunological characteristics of a large series of patients with delayed lupus nephritis (LN). METHODS: A cross-sectional study was carried out. Patients with systemic lupus erythematosus (SLE) who developed renal involvement >or=5 years after the first manifestation(s) of the disease (delayed LN, n = 48) were compared with patients with SLE in whom LN developed within 5 years or less after SLE appeared (early-onset LN, n = 187). A control group, the no LN (NLN) group, comprised patients with longstanding SLE (duration of disease >10 years) who had never shown signs of renal involvement (n = 164). RESULTS: The group with delayed LN was positively associated with Sjögren's syndrome, lung involvement and antiphospholipid syndrome as compared with early LN. However, its renal clinical expression and histopathological patterns were similar to those of early-onset LN. The frequency of anti-dsDNA, anti-Sm and anti-RNP antibodies was higher in patients with LN than in the NLN group, as was the frequency of low complement levels. Jaccoud's arthropathy was a protective factor for nephritis. CONCLUSIONS: Delayed LN is not uncommon in patients with SLE. The identified risk factors might aid in its diagnosis and enhance the ability to identify patients at risk for this complication of SLE.

Epstein-Barr virus and cytomegalovirus in autoimmune diseases: are they truly notorious? A preliminary report.

To date, it is believed that the origin of autoimmune diseases is one of a multifactorial background. A genetic predisposition, an immune system malfunction or even backfire, hormonal regulation, and environmental factors all play important roles in the pathogenesis of autoimmune diseases. Among these environmental factors, the role of infection is known to be a major one. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are considered to be notorious as they are consistently associated with multiple autoimmune diseases. A cohort of 1595 serum samples, of 23 different autoimmune disease groups, was screened for evidence of prior infection with EBV and CMV. All samples were screened for antibodies against EBV nuclear antigen-1 (IgG), EBV viral capsid antigen (IgG and IgM), EBV early antigen (IgG), EBV heterophile antibody, and CMV (IgG and IgM) antibodies using Bio-Rad's BioPlex 2200. A new association is proposed between EBV and polymyositis, as results show a significant increase in titers of various EBV target analytes when compared with healthy controls. Our results also support prior information suggesting the association between EBV and multiple autoimmune diseases, including SLE, antiphospholipid syndrome, rheumatoid arthritis, multiple sclerosis, pemphigus vulgaris, giant cell arthritis, Wegener's granulomatosis, and polyarteritis nodosa (PAN). Elevated CMV IgG titers were observed in sera of SLE patients. Our data support the theory that EBV is notoriously associated with many autoimmune diseases. CMV appears to be associated to autoimmune diseases as well, yet establishing this theory requires further investigation.

Cholinoreceptor autoantibodies in Sjögren syndrome.

Previous studies have demonstrated that antibodies against cholinoreceptors of exocrine glands correlate with dry mouth in persons with primary Sjögren syndrome (pSS). The aim of the present investigation was to establish if serum IgG antibodies (pSS IgG) were able to interact with cholinoreceptors in rat submandibular gland-dependent stimulation of cyclooxygenase 2 (COX-2) mRNA expression and PGE(2) production. Our findings indicated that pSS IgG-stimulating M(3), M(4), and M(1) cholinoreceptors exerted an increase in COX-2 mRNA without affecting COX-1 mRNA expression and increased PGE(2) production. Inhibitors of phospholipase A(2), COX- s, L-type calcium channel currents, and Ca(2+)-ATPase from sarcoplasmic reticulum prevented the pSS IgG effect on PGE(2) production. An ionophore of calcium mimicked pSS IgG action, suggesting a crucial role of calcium homeostasis in the cholinoreceptor-stimulated increase in PGE(2) production. Moreover, the amounts of PGE(2) in saliva and in sera from persons with pSS were significantly higher than in pre- or post-menopausal women. These findings illustrate the importance of autoantibodies to cholinoreceptors in the generation of chronic inflammation of target tissues in SS.

TNF microsatellites polymorphism is associated with rheumatoid arthritis. Confirming evidence in northwestern Colombians.

OBJECTIVE: To examine the contribution of tumor necrosis factor alpha (TNF) microsatellite (a to e) polymorphism to the genetic risk of developing rheumatoid arthritis (RA) in a northwestern Colombian population. METHODS: This was an association study in which 108 RA patients and 222 matched individuals were enrolled. HLA-DRB1 and DQB1 polymorphisms were evaluated to examine for linkage disequilibrium between these loci and TNF micro- satellites. Genotyping was performed using denaturing polyacrylamide gels and polymerase chain reaction-sequence techniques. RESULTS: By unconditional logistic regression analysis, the TNFa6 allele (OR=2.37, 95%CI 1.07-5.24) and the TNFb4 allele (OR=3.01, 95%CI 1.07-9.00) were observed to be associated with disease. These associations were independent of HLA-DR and HLA-DQ since linkage disequilibrium between HLA class II and TNF microsatellites was not observed. In addition, patients with the TNFa8 allele had a five times greater risk of developing extra-articular manifestations as compared to patients without this allele (OR=5.07, 95%CI 1.14-22.52), regardless of age and the duration of disease. Haplotype analysis disclosed a protective effect for TNFa7/b7/c1/d4/e3/-308G/-238G. CONCLUSION: These results confirm that the TNF locus exerts a primary influence on both susceptibility to and the severity of RA.

Clinical and immunological characteristics of type 1 diabetes mellitus in a northwestern Colombian population.

We underwent a project aimed to define the clinical and immunological characteristics of type 1 diabetes (T1D) in a Colombian population. This was a multicenter and cross-sectional study. Patients were systematically interviewed and their medical records reviewed, using a questionnaire that sought information about demographic, clinical and immunological characteristics. Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase antibodies (IA-2A) and insulin antibodies (IAA) were examined by radioimmunoassay. There were 107 patients with T1D. Male:female ratio was 1:1. Half of the patients developed diabetes ketoacidosis at onset. GADA, IA-2A, and IAA were detected in 45%, 40%, and 69% of the cases, respectively. GADA positive patients were older and had a less duration of disease than patients without these autoantibodies (p<0.01). Association between breast feeding with the presence of antibodies or clinical characteristics was not observed. The results highlight some differences of T1D expression according to geographic location and ethnicity. Differences in age at onset and clinical variables may point to an environmental factor or deficient access to health care system. Genetic studies underway will provide important information in this population. These results might help to define public health policies in our population to improve T1D diagnosis, patients' quality of life and their outcome.