An antibody profile of systemic lupus erythematosus detected by antigen microarray.

SUMMARY: Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states--SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long-term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), Epstein-Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin-like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE.

The impact of rheumatoid foot on disability in Colombian patients with rheumatoid arthritis.

BACKGROUND: Alterations in the feet of patients with rheumatoid arthritis (RA) are a cause of disability in this population. The purpose of this research was to evaluate the impact that foot impairment has on the patients' global quality of life (QOL) based on validated scales and its relationship to disease activity. METHODS: This was a cross-sectional study in which 95 patients with RA were enrolled. A complete physical examination, including a full foot assessment, was done. The Spanish versions of the Health Assessment Questionnaire (HAQ) Disability Index and of the Disease Activity Score (DAS 28) were administered. A logistic regression model was used to analyze data and obtain adjusted odds ratios (AORs). RESULTS: Foot deformities were observed in 78 (82%) of the patients; hallux valgus (65%), medial longitudinal arch flattening (42%), claw toe (lesser toes) (39%), dorsiflexion restriction (tibiotalar) (34%), cock-up toe (lesser toes) (25%), and transverse arch flattening (25%) were the most frequent. In the logistic regression analysis (adjusted for age, gender and duration of disease), forefoot movement pain, subtalar movement pain, tibiotalar movement pain and plantarflexion restriction (tibiotalar) were strongly associated with disease activity and disability. The positive squeeze test was significantly associated with disability risk (AOR = 6,3; 95% CI, 1.28-30.96; P = 0,02); hallux valgus, and dorsiflexion restriction (tibiotalar) were associated with disease activity. CONCLUSION: Foot abnormalities are associated with active joint disease and disability in RA. Foot examinations provide complementary information related to the disability as an indirect measurement of quality of life and activity of disease in daily practice.

TIRAP (MAL) S180L polymorphism is a common protective factor against developing tuberculosis and systemic lupus erythematosus.

BACKGROUND AND AIM: The involvement of Toll-like receptor (TLR)-mediated pathways in infectious and autoimmunity has been suggested. The MyD88 adaptor-like (Mal) protein, also known as the TIR domain-containing adaptor protein (TIRAP), is implicated in the TLR2- and TLR4-mediated MyD88-dependent signaling pathway. The aim of this study was to investigate the influence of the functional TIRAP (MAL) S180L polymorphism on tuberculosis (TB) and four autoimmune diseases namely: rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and type 1 diabetes mellitus (T1D). METHODS: This was a case-control and family based association study in which 1325 individuals from a well-defined Colombian population were involved. TIRAP (MAL) S180L genotyping was done by using a polymerase chain reaction-restriction fragment length polymorphism technique and by direct sequencing. RESULTS: Leu180 allele was found to be a protective factor against developing TB (odd ratio (OR): 0.53, 95% confidence interval (CI): 0.29-0.97) and SLE (OR: 0.29, 95% CI: 0.14-0.61) while no significant influence on RA, pSS and T1D was observed. CONCLUSION: These results support the influence of TIRAP (MAL) S180L polymorphism on TB and indicate that TB and SLE might share a common immunogenetic pathway in the innate immune response.

Risk factors associated with different stages of atherosclerosis in Colombian patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased prevalence of cardiovascular disease (CVD). Since atherosclerosis development is a gradual process of damage inside the artery wall, and the phenotype-genotype correlation of complex diseases may vary depending on ethnicity, we sought to investigate the influence of clinical features, routine inflammatory markers, and the genetic component of RA on different stages of atherosclerosis in northwestern Colombian patients with RA. METHODS: A group of 140 patients with RA were enrolled in this study. All patients underwent a noninvasive evaluation of endothelial function by flow-mediated vasodilation (FMV) and an assessment of carotid intima-media thickness (IMT) by high-resolution B-mode ultrasonography. The patients were classified into 3 categories: endothelial dysfunction (FMV <5%), increased IMT (0.91-1.29 mm), and plaque (IMT >1.30 mm). The risk of being in each category was assessed by investigating traditional and nontraditional cardiovascular risk factors. For each stage of atherosclerosis development, we searched for nontraditional risk factors that were significantly associated with the stage after adjusting for traditional risk factors and current age. RESULTS: Rheumatoid factor seropositivity was significantly associated with endothelial dysfunction (adjusted odds ratio, AOR = 3.0). A duration of RA >10 years (AOR = 29.0) and being a carrier of an HLA-DRB1 shared epitope allele (AOR = 4.8) were associated with atherosclerotic plaque. No association of extra-articular manifestations, anticyclic citrullinated peptide (anti-CCP3) antibodies, and tumor necrosis factor -308 polymorphism with CVD was found. CONCLUSIONS: Our results reveal the presence of RA-related risk factors for CVD which act independently of traditional risk factors. These factors can be used by clinicians to predict CVD in RA patients, and this data should assist in the development of public health policies in our population for the improvement of patient outcomes.