Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies

INTRODUCTION: Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA-protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein-Barr virus in the pathogenesis has been suggested. Similar to Epstein-Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1-70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. METHODS: Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein-Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1-70 k, P peptide, rheumatoid factor, dsDNA, beta2-glycoprotein I). RESULTS: IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV+ group (n = 20) versus the IgM anti-CMV(-)IgG+ (n = 39) group were compared. Most (19/20) of the IgM anti-CMV+ cases were IgG anti-CMV+, consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein-Barr virus-viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV+ group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1-70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA-protein complex (P = 0.0077). CONCLUSIONS : Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis

High prevalence of autoantibodies to RNA helicase A in Mexican patients with systemic lupus erythematosus

Introduction: Autoantibodies to RNA helicase A (RHA) were reported as a new serological marker of systemic lupus erythematosus (SLE) associated with early stage of the disease. Anti-RHA and other autoantibodies in Mexican SLE patients and their correlation with clinical and immunological features were examined.Methods: Autoantibodies in sera from 62 Mexican SLE patients were tested by immunoprecipitation of 35S-labeled K562 cell extract and enzyme-linked immunosorbent assay (anti-U1RNP/Sm, ribosomal P, ?2GPI, and dsDNA). Anti-RHA was screened based on the immunoprecipitation of the 140-kDa protein, the identity of which was verified by Western blot using rabbit anti-RHA serum. Clinical and immunological characteristics of anti-RHA-positive patients were analyzed.Results: Anti-RHA was detected in 23% (14/62) of patients, a prevalence higher than that of anti-Sm (13%, 8/62). Prevalence and levels of various autoantibodies were not clearly different between anti-RHA (+) vs. (-) cases, although there was a trend of higher levels of anti-RHA antibodies in patients without anti-U1RNP/Sm (P = 0.07). Both anti-RHA and -Sm were common in cases within one year of diagnosis; however, the prevalence and levels of anti-RHA in patients years after diagnosis did not reduce dramatically, unlike a previous report in American patients. This suggests that the high prevalence of anti-RHA in Mexican patients may be due to relatively stable production of anti-RHA.Conclusions: Anti-RHA was detected at high prevalence in Mexican SLE patients. Detection of anti-RHA in races in which anti-Sm is not common should be clinically useful. Racial difference in the clinical significance of anti-RHA should be clarified in future studies. � 2010 V�zques-Del Mercado et al; licensee BioMed Central Ltd

Single nucleotid polymorphisms of adhesion molecules and clinical parameters in rheumatoid arthritis [Polimorfismos de nucleótido simple en moléculas de adhesión y parámetros clínicos en artritis reumatoide]

The aim was to investigate the relationship between E-selectin, ICAM1 and VCAM1 polymorphisms with lipid profile and rheumatoid arthritis (RA) clinical inflammation markers. Sixty RA patients classified according to 1987 American College of Rheumatology (ACR) criteria and 60 unrelated healthy controls (HS) defined as Mexican-mestizo population, were included. The genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) technique. The ESR (erythrocyte sedimentation rate), RF (rheumatoid factor), fibrinogen (FB), C-reactive protein (CRP) and lipid profile were measured by routine methods. Statistical analysis was performed using SPSS v10.0. The significant Pearson's correlations were: ESR with CRP, RF, FB and HDLc, (r=0.507, 0.296, 0.475, and -0.308, respectively); CRP with FB (r=0.613), p<0.05. The results showed an association with A allele of ICAM1 polymorphism and serum levels of HDLc and LDLc; and Apo-B and FR showed an association with C allele of VCAM1 polymorphism (p<0.05). Data shows that FB and HDLc levels, and ICAM1 polymorphism allele 721A and VCAM1 polymorphism allele 1238G are associated with clinical inflammation markers in RA. Our Mexican-mestizo population showed differences with many reports (from English, American, Turkish, Japanese, Chinese, Italian, and Korean populations)

Single nucleotid polymorphisms of adhesion molecules and clinical parameters in rheumatoid arthritis [Polimorfismos de nucleótido simple en moléculas de adhesión y parámetros clúnicos en artritis reumatoide]

The aim was to investigate the relationship between E-selectin, ICAM1 and VCAM1 polymorphisms with lipid profile and rheumatoid arthritis (RA) clinical inflammation markers. Sixty RA patients classified according to 1987 American College of Rheumatology (ACR) criteria and 60 unrelated healthy controls (HS) defined as Mexican-mestizo population, were included. The genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) technique. The ESR (erythrocyte sedimentation rate), RF (rheumatoid factor), fibrinogen (FB), C-reactive protein (CRP) and lipid profile were measured by routine methods. Statistical analysis was performed using SPSS v10.0. The significant Pearson's correlations were: ESR with CRP, RF, FB and HDLc, (r=0.507, 0.296, 0.475, and -0.308, respectively); CRP with FB (r=0.613), p<0.05. The results showed an association with A allele of ICAM1 polymorphism and serum levels of HDLc and LDLc; and Apo-B and FR showed an association with C allele of VCAM1 polymorphism (p<0.05). Data shows that FB and HDLc levels, and ICAM1 polymorphism allele 721A and VCAM1 polymorphism allele 1238G are associated with clinical inflammation markers in RA. Our Mexican-mestizo population showed differences with many reports (from English, American, Turkish, Japanese, Chinese, Italian, and Korean populations)

Expression of ICAM1 and VCAM1 serum levels in rheumatoid arthritis clinical activity. Association with genetic polymorphisms

To investigate the association of sICAM-1 and sVCAM-1 with ICAM1 721G>A and VCAM1 1238G>C polymorphisms and rheumatoid arthritis (RA) clinical activity, sixty RA patients and 60 healthy non-related subjects (HS) matched for age and sex were recruited. Soluble adhesion molecules were determined by ELISA technique. Rheumatoid factor (RF), C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured by routine methods. Disability and clinical activity was measured with Spanish-HAQ-DI and DAS28 scores, respectively. The ICAM1 and VCAM1 polymorphism were identified using the PCR-RFLP procedure. Inter-group comparison showed increased levels of sICAM-1 and sVCAM-1 in RA patients (284 and 481 ng/mL) versus HS (132 and 280 ng/mL); in the RA group, significant correlations between sVCAM-1 and RF (r = 0.402), ESR (r = 0.426), Spanish-HAQ-DI (r = 0.276), and DAS28 (r = 0.342) were found, whereas sICAM-1 only correlated with RF (r = 0.445). In RA patients, a significant association with the 721A allele of ICAM1 polymorphism (p = 0.04), was found. In addition, the allele impact (G/A+A/A) of this polymorphism was confirmed, (p = 0.038, OR = 2.3, C.I. 1.1-5.0). sVCAM-1 and sICAM-1 serum levels reflected the clinical status in RA, independently of the ICAM1 and VCAM1 polymorphism. However, the ICAM1 721A allele could be a genetic marker to RA susceptibility. © 2009 IOS Press and the authors. All rights reserved

Early retinopathy of prematurity findings identified with fluorescein angiography

Background: Fluorescein angiography has been fundamental for the understanding and description of vascular disorders affecting the retina and choroid. The aim of this report is to assess the early anatomic retinal changes visible with angiography, and their relation with the clinical findings of retinopathy of prematurity. Methods: Ten babies were included in the study, the initial examination being at 2 weeks after birth. Two cycles of tropicamide 0.8 % and phenylephrine 5 % eye drops were instilled into both eyes 30 min before examination. A RetCam II was used to obtain digital retinal images, after instilling topical anesthesia (tetracain 0.5 %) and using a contact gel. Fluorescein angiography was undertaken following administration of an intravenous bolus of 0.1 ml/kg saline fluorescein 10 % followed by a 3.0-ml isotonic saline flush, with the assistance of the neonatologist; the right and left eyes were imaged. Results: We observed that some of the vascular abnormalities described for threshold disease by Lepore were already present at the second week of life, preceding the diagnosis of threshold disease by 3-4 weeks in two cases. The main findings in our cases were arterio-venous shunts, surrounded by areas of capillary non-perfusion, rosary-bead-like hyper-fluorescence, tortuosity and leakage from distal arterioles, none of which were detectable in the digital fundus pictures. Conclusions: Early ROP screening at the NICU that includes FA is a safe procedure, and gives the examiner details of vascular changes that are not detectable by indirect ophthalmoscopy, which could predict the progression to threshold disease, and provide an alert about the need of therapeutic interventions. © 2013 Springer-Verlag Berlin Heidelberg