The clinical significance of posttranslational modification of autoantigens.

Posttranslational modifications (PTMs) are defined as covalent modifications occurring in a specific protein amino acid in a time- and signal-dependent manner. Under physiological conditions, proteins are posttranslationally modified to carry out a large number of cellular events from cell signaling to DNA replication. However, an absence, deficiency, or excess in PTMs of a given protein can evolve into a target to trigger autoimmunity, since PTMs arise in the periphery and may not occur in the thymus; hence, proteins with PTMs never tolerize developing thymocytes. Consequently, when PTMs arise during cellular responses, such as inflammation, these modified self-antigens can be taken up and processed by the antigen-presenting cells (APCs). Autoreactive T cells, which recognize peptides presented by APCs, can then infiltrate into host tissue where the modified antigen serves to amplify the autoimmune response, eventually leading to autoimmune pathology. Furthermore, a PTM occurring in an amino acid residue can induce changes in the net charge of the protein, leading to conformational modifications in the tertiary and quaternary structure of the protein, especially interaction with human leukocyte antigen (HLA) molecules. Molecular mimicry (MM) was until now the prevailing hypothesis explaining generation of autoimmunity; nevertheless, experimental animal models need inflammation via infection or other immunogens to ensure autoimmunity; MM alone is not sufficient to develop autoimmunity. PTMs could arise as an additive factor to MM, which is required to start an autoimmune response. PTMs have been found to be present in different pathologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, and primary biliary cirrhosis. The aim of the present review is to expose protein posttranslational modifications and the evidence suggesting their role in the generation of autoimmunity.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor sera titers in leprosy patients from Mexico.

Leprosy offers a broad spectrum of altered immunological sceneries, ranging from strong cell-mediated immune responses seen in tuberculoid leprosy (TT), through borderline leprosy (BB), to the virtual absence of T cell responses characteristic in lepromatous leprosy (LL). The exact mechanism of autoantibodies production remains unknown in leprosy and other chronic inflammatory diseases and also the contribution of these antibodies to the pathogenesis of the disease. The aim of this study is to evaluate the frequency and profiles of serum anti-cyclic citrullinated peptide antibodies (a-CCP), rheumatoid factor (RF) and its relationship with leprosy spectrum. Serum samples from 67 leprosy patients (54 LL, 5 TT and 8 BB) and 46 clinically healthy subjects (CHS) from the same endemic region were investigated. The clinical chart and questionnaire were used to obtain clinical information. Anti-cyclic citrullinated peptide antibodies (a-CCP) were measured by enzyme-linked immunosorbent assay, whereas the rheumatoid factor (RF) levels were measured by nephelometric method. The mean age of patients was 51.5 ± 13 years. Sera levels of a-CCP where higher in leprosy patients than in CHS (5.9 ± 11.6 vs. 0.3 ± 0.29) (P < 0.0001); the same pattern was found for RF sera titers without reaching statistical significance (16.8 ± 22.5 vs. 9.9 ± 3) (P = NS). We did not find a correlation between a-CCP and RF Rho =0.02786 (IC 95%) P = 0.8229. However, LL patients had higher a-CCP and RF levels than TT patients. Although an absence in correlation was observed, the serum levels of a-CCP antibodies and RF appeared to be useful in distinguishing LL from TT patients with a limited significance in detecting reactional leprosy patients.

The clinical significance of coagulation and the inflammatory response in autoimmunity.

Maintenance of normal blood flow requires equilibrium between procoagulant and anticoagulant factors; occasionally, procoagulant activity predominates, leading to clot formation; frequently, tissue damage is the triggering factor. Hereditary factors, primary or acquired, play a role in the development of thrombosis. Primary thrombophilia is associated with hereditary factors, which promote hypercoagulability because natural anticoagulants are not exerting their activity. On the other hand, acquired thrombophilia may occur associated to autoimmune diseases, cancer, surgical procedures, pregnancy, postpartum period, and obesity. Activation of the coagulation system is characterized by the co-participation of inflammatory response components, factors related to the subjacent disease, and other procoagulant factors. The study of patients with thrombosis should include both inflammatory and autoimmune response markers.

Serologic features of primary Sjögren's syndrome: clinical and prognostic correlation.

Sjögren's syndrome (SS) is a chronic inflammatory systemic autoimmune disease. The disease spectrum extends from sicca syndrome to systemic involvement and extraglandular manifestations, and SS may be associated with malignancies, especially non-Hodgkin's lymphoma. Patients with SS present a broad spectrum of serologic features. Certain serological findings are highly correlated with specific clinical features, and can be used as prognostic markers.

Influence of prevalent vertebral fractures on the quality of life of patients with systemic lupus erythematosus.

BACKGROUND: The prevalence of vertebral fractures in systemic lupus erythematosus (SLE) ranges between 20% and 21.4%, and patients with these fractures have impaired walking and activities of daily living. Moreover, clinical and radiological vertebral fractures have been associated with increased mortality. OBJECTIVES: To compare the quality of life of patients with SLE with and without vertebral fractures. METHODS: The study group comprised 140 women with SLE undergoing screening for vertebral fractures using a standardized method. SLE disease activity and organ damage were measured by the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI) and the Systemic International Collaborating Clinics/American College of Rheumatology damage index (SLICC), respectively. The QUALEFFO and Center for Epidemiologic Studies Depression Scale were used to measure health-related quality of life and depression, respectively. RESULTS: The median age of the 140 patients was 43 years (range 18-76); disease duration was 72 months (range 6-432); 49.7% were menopausal. Thirty-four patients (24.8%) had vertebral fractures (> or = 1), mostly in the thoracic spine. Patients with vertebral fractures had a higher mean age (49.5 +/- 13.4 vs. 41 - 13.2 years, P= 0.001) and disease damage (57.1% vs. 34.4%, P = 0.001). The global QUALEFFO score was not different between the vertebral fractures group and the non-vertebral group. The only significant difference in the QUALEFFO items was in physical function (P = 0.04). A significant correlation was found between the severity of vertebral fractures and the QUALEFFO pain (r = 0.27, P = 0.001) and physical function (r = 0.37, P = 0.02) scores. The number of vertebral fractures correlated only with physical function (r = 0.01). CONCLUSIONS: The HRQOL of women with SLE is low, regardless of whether they have vertebral fractures or not, but patients with vertebral fractures have worse physical function compared to those without. Strategies to improve the HRQOL of patients with SLE with or without vertebral fractures are necessary.

[Anesthesiologist's aptitude for peri-operative detection and treatment of latex allergy]. / Aptitud del anestesiólogo para la detección y tratamiento perioperatorios de la alergia al látex.

BACKGROUND: Latex allergy is the second cause of perioperative anaphylaxis. Anesthesiologists play a key role in opportune identification of risk factors, as well as clinical diagnosis and therapeutic management. OBJECTIVE: To evaluate the anesthesiologists aptitude to identify and treat latex allergy. PARTICIPANTS AND METHODS: Sixty-six anesthesiologists from five general hospitals located at Guadalajara, Jalisco, Mexico, were evaluated. Aptitude was determined by applying a validated structured instrument. Aptitude levels were measured by using an ordinal scale. Comparisons were performed using Mann Whitney U test. RESULTS: Anesthesiologist's global aptitude ranged from -2 to 27 with a median of 8 (from a maximum value in the scale of 40); frequencies by each category of the scale were: Random 48 (72.7%), Very bad 11 (16.7%), Bad 4 (6.1%) and Medium only 3 (4.5%). Both Good and Very good categories registered no anesthesiologist. The relationship of this indicator with other variables did not reach statistical significance (KW 6.478; p = 0.16617). CONCLUSIONS: A suboptimal aptitude was identified among anesthesiologists regarding identification of latex allergy. A need to establish new strategies for educative intervention in order to improve this issue was identified.

[Assessment of serum IgG activity correlation against cyclic citrullinated peptide antibodies, topoisomerase I and centromere proteins in Mexican patients with progressive systemic sclerosis]. / Evaluación de la correlación de la actividad de IgG sérica contra péptido citrulinado cíclico, topoisomerasa I y proteínas de centrómero en pacientes mexicanos con esclerosis sistémica progresiva.

OBJECTIVE: To evaluate sera titers for antibodies anti-cyclic citrullinated peptide and their correlation against sera levels of anti-topoisomerase I and anti-centromere antibodies in Mexican patients with systemic sclerosis. PATIENTS AND METHODS: Consecutive outpatients with systemic sclerosis who attending to rheumatology clinic at a second level hospital facility. The antibodies anti-cyclic citrullinated peptide, anti-topoisomerase I and anti-centromere were determined by enzymatic immunoassay (ELISA). STATISTICAL ANALYSIS: Spearman for correlation between numerical variables with nonparametric distribution. Fisher exact test or chi2 to compare proportions and Student t test for dimensional variables. RESULTS: Thirty female patients were included; aged 53 +/- 13, the disease duration at the time of the study was 10 +/- 9. Twenty-three patients (77%) exhibited diffuse disease. Anti-centromere, anti-topoisomerase I, and anti-cyclic citrullinated peptide were detected in nine, nine and three patients respectively. The correlation analysis showed the independence of autoantibodies anti-centromere and anti-topoisomerase I with respect to the levels of anti-cyclic citrullinated peptide. CONCLUSIONS: This study confirms the low frequency of anti-cyclic citrullinated peptide antibodies in patients with systemic sclerosis. A lack of correlation between autoantibodies considered as "mutually excluded" anti-topoisomerase I and anti-centromere, indicating that the analysis of the relevance for anti-cyclic citrullinated peptide in systemic sclerosis must include other clinical and serological variables.

Therapeutic options in autoimmune myasthenia gravis.

Autoimmune myasthenia gravis (MG) is associated with circulating antibodies to AChR, modification of the synaptic cleft, and destruction of the postsynaptic neuromuscular membrane. The hallmark is fluctuating muscular weakness and fatigability of muscles on sustained repeated activity. Various drugs and invasive procedures have been used in the treatment of MG including acetylcholinesterase inhibitors, corticosteroids, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, tacrolimus, etanercept, intravenous immunoglobulin, plasma exchange and thymectomy. We review the role of each of these drugs and invasive procedures in MG. Although current treatment is highly successful and mortality is almost nil, further trials are required to identify the most suitable treatments for different subgroups of MG patients. In addition, safer and more potent drugs are required as most current drugs have major side effects due to immunosuppression. Therefore, the goal of novel therapies should be increased specificity of the immune-directed agents.

[Correlation between serum levels of antistreptolysin O and C reactive protein]. / Correlación entre concentraciones séricas de anti-estreptolisina O y proteína C reactiva.

INTRODUCTION: Measurement of antibodies to extracellular products of group A streptococcus, specifically streptolysin O (ASO), is useful to detect previous streptococcal infection, besides its ability to identify those asymptomatic carriers or to support diagnosis of poststreptococcal disease. An inflammatory process has been considered as a one variable that could be modifying the interpretation of ASO test. OBJECTIVE: identify in serum from clinically healthy subjects the covariability of antibodies to streptolysin O (ASO) serum concentration, high sensitivity C reactive protein (hsCRP). METHODS: 87 serum samples from 87 clinically healthy subjects were tested. ASO, hsCRP, and total IgG were measured by nephelometry. Statistical analysis was performed using mean, median, and standard deviation with descriptive purpose; in addition, normality of the distribution of variables was determined. Spearman correlation test was performed in all cases. Significance was considered for p < or = 0.05. RESULTS: A non-parametric distribution was exhibited by both ASO and hsCRP values. Gaussian distribution was finding only for IgG values. Spearman correlation values for ASO against both hsCRP and IgG were 0.19 (p = NS). CONCLUSIONS: ASO values distribution did not correlate with dispersion of levels of hsCRP, neither IgG. This suggests that values obtained from clinically healthy subjects in this study where not modified influenced by a potential subjacent inflammatory process, neither IgG serum levels.

Pathophysiology of Sjögren's syndrome.

The term Sjögren's syndrome refers to keratoconjunctivitis sicca and xerostomia due to lymphocytic infiltrates of lachrymal and salivary glands. The current used criteria for diagnosis of primary Sjögren's syndrome is the American-European consensus. Primary Sjögren's syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lachrymal glands and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. The infiltrating cells (T- and B-cells, dendritic cells) interfere with glandular function at several points: destruction of glandular elements by cell-mediated mechanisms; secretion of cytokines that activate pathways bearing the signature of type 1 and 2 interferons; production of autoantibodies that interfere with muscarinic receptors; and secretion of metalloproteinases (MMPs) that interfere with the interaction of the glandular cell with its extracellular matrix, which is necessary for efficient glandular function. As the process progresses, the mucosal surfaces become sites of chronic inflammation and the start of a vicious circle. Despite extensive study of the underlying cause of Sjögren's syndrome, the pathogenesis remains obscure. In broad terms, pathogenesis is multifactorial; environmental factors are thought to trigger inflammation in individuals with a genetic predisposition to the disorder.