Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients

This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39–7.42), p 0.006; HR 18.28 (2.80–119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.     

MMP-1 drives immunopathology in human tuberculosis and transgenic mice

Mycobacterium tuberculosis can cause lung tissue damage to spread, but the mechanisms driving this immunopathology are poorly understood. The breakdown of lung matrix involves MMPs, which have a unique ability to degrade fibrillar collagens at neutral pH. To determine whether MMPs play a role in the immunopathology of tuberculosis (TB), we profiled MMPs and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs), in sputum and bronchoalveolar lavage fluid from patients with TB and symptomatic controls. MMP-1 concentrations were significantly increased in both HIV-negative and HIV-positive patients with TB, while TIMP concentrations were lower in HIV-negative TB patients. In primary human monocytes, M. tuberculosis infection selectively upregulated MMP1 gene expression and secretion, and Ro32-3555, a specific MMP inhibitor, suppressed M. tuberculosis-driven MMP-1 activity. Since the mouse MMP-1 ortholog is not expressed in the lung and mice infected with M. tuberculosis do not develop tissue destruction equivalent to humans, we infected transgenic mice expressing human MMP-1 with M. tuberculosis to investigate whether MMP-1 caused lung immunopathology. In the MMP-1 transgenic mice, M. tuberculosis infection increased MMP-1 expression, resulting in alveolar destruction in lung granulomas and significantly greater collagen breakdown. In summary, MMP-1 may drive tissue destruction in TB and represents a therapeutic target to limit immunopathology.     

Additional evidence to support the phasing-out of treatment category II regimen for pulmonary tuberculosis in Peru

The effectiveness of the World Health Organization's (WHO) treatment category II regimen for tuberculosis in 124 patients was compared to that of 1147 patients receiving treatment category I in Lima, Peru following WHO's guidelines. Drug susceptibility test was available for 85% of patients. Prevalence of multi drug resistance and streptomycin resistance were 5.1% and 20.7%, respectively. Overall cure rate for regimen II was lower than that of regimen I: 67.8% (95% CI: 58.9-75.6.) vs 77.8% (95% CI: 75.3-80.2), p=0.014. Multi-drug resistance exerted a profound effect on cure rates in both regimens. Our results support the phasing-out of treatment category II regimen in Peru.     

Private sector contributions and their effect on physician emigration in the developing world

The contribution made by the private sector to health care in a low- or middle-income country may affect levels of physician emigration from that country. The increasing importance of the private sector in health care in the developing world has resulted in newfound academic interest in that sector’s influences on many aspects of national health systems. The growth in physician emigration from the developing world has led to several attempts to identify both the factors that cause physicians to emigrate and the effects of physician emigration on primary care and population health in the countries that the physicians leave. When the relevant data on the emerging economies of Ghana, India and Peru were investigated, it appeared that the proportion of physicians participating in private health-care delivery, the percentage of health-care costs financed publicly and the amount of private health-care financing per capita were each inversely related to the level of physician expatriation. It therefore appears that private health-care delivery and financing may decrease physician emigration. There is clearly a need for similar research in other low- and middle-income countries, and for studies to see if, at the country level, temporal trends in the contribution made to health care by the private sector can be related to the corresponding trends in physician emigration. The ways in which private health care may be associated with access problems for the poor and therefore reduced equity also merit further investigation. The results should be of interest to policy-makers who aim to improve health systems worldwide.     

Genetics of ANCA-associated Vasculitides

The distribution of the anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is not uniform across geographical regions and ethnic and racial groups, suggesting that genetic and environmental factors affect the pathogenesis of these diseases. In addition, genetic factors affect not only the clinical syndrome phenotypes and their prognosis, but also ANCA specificity; these data suggest that AAV may need reclassification. Several genes have been evaluated, including ANCA targets and those of the immune system, for example co-stimulatory molecules, signaling regulators, cytokines, Fc and other receptors, and other proteins. This article provides a review of genetic factors affecting the pathogenesis and prognosis of AAV. Further studies to determine the effect of genetic factors on the clinical syndrome phenotypes and ANCA specificity need to be performed across different ethnic groups.     

Abatacept for the treatment of systemic lupus erythematosus

Introduction: Due to improvements in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), several target drugs have been and are being developed. One of the possible targets in SLE is co-stimulation between antigen-presenting cells and T cells. Abatacept is a co-stimulation moderator approved for the treatment of several autoimmune diseases. There is an unmet need for drugs with a better efficacy and safety profile when treating patients with SLE.

Areas covered: In this review, the authors discuss the mechanism of action of abatacept including its role in the immune system and glomeruli, and relevant information about its clinical efficacy and safety. Possible explanations for the failure of previous randomized clinical trials are also discussed.

Expert opinion: Abatacept has demonstrated efficacy in other autoimmune diseases, but in SLE, randomized clinical trials have failed to achieve their primary outcome. Despite these disappointing results and based on its mechanism of action, abatacept seems to have a role in lupus nephritis and arthritis. This should be corroborated with new trials which hopefully will overcome the design pitfalls of the ones conducted to date.     

Predictors of hospitalization for COVID-19 in patients with autoimmune rheumatic diseases: results from a community cohort follow-up

Clinical Rheumatology - The identification of risk factors for COVID-19 adverse course in autoimmune rheumatic diseases (ARDs) is of the utmost importance when approaching patient management;...