Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN’s multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.
Introduction: Autoantibodies and clinical manifestations in polymyositis/dermatomyositis (PM/DM) are affected by both genetic and environmental factors. The high prevalence of DM and anti-Mi-2 in Central America is thought to be associated with the high UV index of the area. The prevalences of autoantibodies and the clinical manifestations of PM/DM were evaluated comparing two cohorts in Mexico. Methods: Ninety-five Mexican patients with PM/DM (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were studied. Autoantibodies were characterized by immunoprecipitation using 35S-methionine labeled K562 cell extract. Clinical information was obtained from medical records. Results: DM represented 69% of PM/DM and anti-Mi-2 was the most common autoantibody (35%), followed by anti-p155/140 (11%); however, anti-Jo-1 was only 4%. The autoantibody profile in adult-onset DM in Mexico City versus Guadalajara showed striking differences: anti-Mi-2 was 59% versus 12% (P = 0.0012) whereas anti-p155/140 was 9% versus 35% (P = 0.02), respectively. A strong association of anti-Mi-2 with DM was confirmed and when clinical features of anti-Mi-2 (+) DM (n = 30) versus anti-Mi-2 (-) DM (n = 36) were compared, the shawl sign (86% versus 64%, P < 0.05) was more common in the anti-Mi-2 (+) group (P = 0.0001). Levels of creatine phosphokinase (CPK) were higher in those who were anti-Mi-2 (+) but they responded well to therapy. Conclusions: Anti-Mi-2 has a high prevalence in Mexican DM and is associated with the shawl sign and high CPK. The prevalence of anti-Mi-2 and anti-p155/140 was significantly different in Mexico City versus Guadalajara, which have a similar UV index. This suggests roles of factors other than UV in anti-Mi-2 antibody production.
In patients with head and neck cancer, malnutrition is common. Most cases are treated by chemo-radiotherapy and surgery, with adverse effects on the aerodigestive area. Clinical and biochemical characteristics, health-related quality of life, survival, and risk of death were studied. The selected subjects were divided into normal- and low-phase-angle (PA) groups and followed up for at least two years. Mean ages were 67.2 and 59.3 years for low and normal PA, respectively. Patients with PA < 4.42° had significant differences in age, anthropometric and biochemical indicators of malnutrition, and inflammatory status compared to patients with PA > 4.42°. Statistical differences were found in the functional and symptom scales, with lower functional scores and higher symptom scores in patients with low PA. Median survival was 19.8 months for those with PA < 4.42° versus 34.4 months for those with PA > 4.42° (p < 0.001).The relative risk of death was related to low PA (2.6; p < 0.001). The percentage of living patients (41.7%) is almost the same as the percentage of deceased subjects (43.1%; p = 0.002), with high death rates in patients with PA < 4.42°. Phase angle was the most crucial predictor of survival and a risk factor for death in the studied cases.
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, β2GPI, 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.
Leptin has a prominent role in the development and maintenance of acute and chronic inflammatory states such as rheumatoid arthritis (RA) and obesity. Nevertheless, the association of serum leptin (sLep) and soluble leptin receptor (sLepR) in RA pathogenesis has not been clarified. The purpose of this study was to evaluate the association of sLep, sLepR and leptin production indexes such as sLep/fat mass ratio with clinical activity and biomarkers and anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA compared with body mass index (BMI) matched control subjects. We included 64 RA patients and 66 controls matched for age, gender and BMI. Subjects were evaluated for BMI, fat mass distribution, sLep, sLepR, sLep/fat mass ratio and sLepR/fat mass ratio. Patients were evaluated for clinical activity and anti-CCP antibodies. We found two or three fold increased sLep levels, sLep/sLepR ratio and sLep/fat mass ratio in obese anti-CCP positive RA patients vs. controls. Partial correlations showed that anti-CCP antibodies were correlated with sLep/fat mass ratio (partial r = 0.347, P = 0.033) after adjustment for age, subcutaneous adipose tissue and fat mass. In preobese and obese RA patients there is and increased production of sLep according to anti-CCP positivity. This phenomenon suggests there is an additive effect of chronic inflammation resulting from RA and obesity in which leptin favors the humoral response against citrullinated proteins. In summary, the data observed in our study suggests sLep could be a surrogate marker of chronicity and humoral immunity in RA in the presence of obesity.
Up to 60% of colorectal cancer (CRC) patients develop malnutrition, affecting treatment effectiveness, increasing toxicity, postoperative complications, hospital stay, and worsening health-related quality of life (HRQOL). This cross-sectional study analyzed data from 48 women and 65 men with CRC. We correlated scores of the scales from the questionnaires EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30 (QLQ)-C30 and Colorectal Cancer module Colorectal 29 (QLQ-CR29) with patients’ body composition and clinical and biochemical indicators of nutritional status. Results: Scores on quality of life were negatively associated with the lymphocyte count (rP = −0.386) and the fat trunk percentage (rP = −0.349) in the women’s group. Scores on the physical and role functioning were inversely associated with the adiposity percentage (rP = −0.486 and rP = −0.411, respectively). In men, total skeletal muscle mass (SMM) was positively associated with emotional functioning (rP = 0.450); the trunk SMM was negatively related to fatigue (rP = −0.586), nausea and vomiting (rP = −0.469), pain (rP = −0.506), and financial difficulties (rP = −0.475); additionally, serum albumin was positively related to physical, emotional, and social functioning scales (rPs = 0.395, 0.453, and 0.363, respectively) and negatively to fatigue (rP = −0.362), nausea and vomiting (rP = −0.387), and appetite loss (rP = −0.347). Among the men, the reduced SMM and biochemical, nutritional parameters were related to low scores on the EORTC QLQ-C30 and QLQ-CR29 functioning scales. In conclusion, in patients with CRC, malnourishment could have a profound effect on the patients’ functionality and QoL (quality of life).