Clinical characterization of a cohort of patients treated for systemic lupus erythematosus in Colombia: A retrospective study.

INTRODUCTION: Systemic lupus erythematosus is an autoimmune disease associated with serious complications and high costs. The aim was to describe the clinical characteristics and health care resource utilization of a Colombian systemic lupus erythematosus outpatient cohort. METHODS: This was a retrospective descriptive study. Clinical records and claims data for systemic lupus erythematosus patients from ten specialized care centers in Colombia were reviewed for up to 12 months. Baseline clinical variables, Systemic Lupus Erythematosus Disease Activity Index, drug use, and direct costs were measured. Descriptive statistics were analyzed using SPSS. RESULTS: A total of 413 patients were included; 361 (87.4%) were female, and the mean age was 42 ± 14 years. The mean disease evolution was 8.9 ± 6.0 years; 174 patients (42.1%) had a systemic manifestation at baseline, mostly lupus nephritis (105; 25.4%). A total of 334 patients (80.9%) had at least one comorbidity, mainly antiphospholipid syndrome (90; 21.8%) and hypertension (76; 18.4%). The baseline Systemic Lupus Erythematosus Disease Activity Index score was 0 in 215 patients (52.0%), 1-5 in 154 (37.3%), 6-10 in 41 (9.9%) and 11+ in 3 (0.7%). All patients received pharmacological therapy, and the most common treatment was corticosteroids (293; 70.9%), followed by antimalarials (chloroquine 52.5%, hydroxychloroquine 31.0%), immunosuppressants (azathioprine 45.3%, methotrexate 21.5%, mycophenolate mofetil 20.1%, cyclosporine 8.0%, cyclophosphamide 6.8%, leflunomide 4.8%) and biologicals (10.9%). The mean annual costs were USD1954 per patient/year, USD1555 for antirheumatic drugs (USD10,487 for those with biologicals), USD86 for medical visits, USD235 for drug infusions and USD199 for laboratory tests. CONCLUSIONS: Systemic lupus erythematosus generates an important economic and morbidity burden for the Colombian health system. Systemic lupus erythematosus outpatient attention costs in the observation year were mainly determined by drug therapy (especially biologics), medical visits and laboratory tests. New studies addressing the rate of exacerbations, long-term follow-up or costs related to hospital care are recommended.

Personalized medicine. Closing the gap between knowledge and clinical practice.

Personalized medicine encompasses a broad and evolving field informed by a patient distinctive information and biomarker profile. Although terminology is evolving and some semantic interpretations exist (e.g., personalized, individualized, precision), in a broad sense personalized medicine can be coined as: "To practice medicine as it once used to be in the past using the current biotechnological tools." A humanized approach to personalized medicine would offer the possibility of exploiting systems biology and its concept of P5 medicine, where predictive factors for developing a disease should be examined within populations in order to establish preventive measures on at-risk individuals, for whom healthcare should be personalized and participatory. Herein, the process of personalized medicine is presented together with the options that can be offered in health care systems with limited resources for diseases like rheumatoid arthritis and type 1 diabetes.

Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab.

The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM(+) and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM(+), switched (IgA(+)/IgG(+)), IgM(+) only, IgD(+) only, and CD27- (IgA(+)/IgG(+)/IgM(+))] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.

Prevalence and clinical features of multiple sclerosis in Latin America.

Multiple sclerosis (MS) in Latin America (LA) is considered to have a low to medium prevalence. However, accurate information on MS in LA is scarce. The aim of this study was to compare clinical characteristics among LA patients through a systematic review of the literature. A systematic search (Spanish, Portuguese and English) was done for all clinical studies of MS in humans (MEDLINE, PubMed, Scielo, BIREME, EMBASE and LILACS) up to May 2011 being focused on a well-defined Latin American population (peer-reviewed journal) following the MOOSE guidelines. The search strategy included combinations of different Mesh terms (two independent researchers). Classification of each article by using the Oxford Centre for Evidence-based Medicine - Levels of Evidence was done. The total number of patients per country for each specific characteristic was compiled. Chi-square test was used to compare the characteristics in the studies retrieved per country. There were 38 articles fulfilling the inclusion criteria, accounting for 4524 patients. Relapsing-remitting form was the most frequent in LA patients and the main initial symptom was motor, followed by optic neuritis and sensorial. A mild expanded disability status scale was the most prevalent in all LA countries. Factors accounting for differences in distribution and clinical course across LA countries include genetics, environment, diagnostic techniques, socioeconomic structure and medical facilities.

Primary biliary cirrhosis and the nuclear pore complex.

Experimental models of autoimmune diseases have led to the conclusion that an immune response to nuclear antigens is a sentinel marker for loss of tolerance and potential tissue damage. Various proteins are targets of antinuclear antibodies in a variety of autoimmune diseases, ranging from systemic rheumatologic disorders to diseases affecting specific organs such as the liver. Autoantibodies against specific nuclear constituents have also been used as probes to understand the structure and the function of the targeted components and their relevance to disease pathogenesis. Approximately a quarter of patients with primary biliary cirrhosis (PBC) have antibodies targeting proteins of the nuclear pore complex (NPC), a multi-protein structure that mediates molecular transport across the nuclear envelope. Autoantibodies against the integral membrane glycoprotein gp210 and nucleoporin p62 appear to be highly specific for PBC, an autoimmune disease characterized by progressive destruction of intrahepatic biliary epithelial cells. This review discusses the diagnostic and clinical relevance of anti-NPC antibodies in PBC and the possibility that this autoimmune response may arise as a result of molecular mimicry.

IgM predominance in autoimmune disease: genetics and gender.

The role of specific immunoglobulin isotypes in human autoimmune disease has long attracted attention. Indeed, the presence of a polyclonal gammopathy is well known in a variety of systemic autoimmune diseases and is likely the result of chronic inflammation. However, in specific clinical situations, patients manifest isolated and elevated IgM levels, but normal IgG and IgA. The pathophysiology of this elevation and the clinical significance have been elusive. However, the relationships between specific genes and hyper-IgM are now very well defined, as it has been documented in primary hyper IgM syndromes. In this review we present data on clinical diseases with characteristic IgM abnormalities, including primary and secondary hyper IgM syndromes, autoimmune hemolytic anemia, cryoglobulinemia, primary biliary cirrhosis and multiple sclerosis and place the data in the perspective of the normal maturation of the immune response, including somatic mutation and genetic rearrangement.

A TGF-beta mediated regulatory mechanism modulates the T cell immune response to rotavirus in adults but not in children.

Children with acute RV-gastroenteritis (GE) had low or undetectable levels of circulating IFN-gamma(+), IL-13(+), IL-2(+), IL-10(+) or IL-17(+) RV-T cells. IFN-gamma(+) T cells and low frequencies of IL-10(+) and IL-2(+) CD4(+) T cells were found in adults with RV-GE during acute and convalescence phases, respectively. Circulating single IFN-gamma(+)>double IFN-gamma(+)/IL-2(+)>single IL-2(+)RV-CD4(+)T cells were observed in healthy adults. In this group, frequencies of IFN-gamma(+) RV-T cells increased after removing CD25(+)cells, blocking TGF-beta with its natural inhibitor, LAP, or inhibiting TGF-betaRI signalling pathway with ALK5i. The frequencies of IFN-gamma(+) RV-T cells were also incremented in PBMC depleted of CD25(+)cells and treated with ALK5i, suggesting that TGFbeta inhibition may be independent of Treg cells. The ALK5i effect was observed in adults but not in children with RV-GE, who had normal numbers of TGF-beta+ Treg cells. Thus, a TGF-beta-mediated regulatory mechanism that modulates RV-T cells in adults is not evident in children.

Factors influencing polyautoimmunity in systemic lupus erythematosus.

OBJECTIVE: Since characterization of the extent to which particular combinations of autoimmune diseases (ADs) occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms, polyautoimmunity (i.e., ADs co-occurring within patients) in systemic lupus erythematosus (SLE) and its associated factors were investigated. METHODS: This was a cross-sectional study in which 335 consecutive patients with SLE and the history of 22 ADs were investigated. A multivariate analysis was performed. A systematic literature review was done and results were grouped by hierarchical cluster procedure analysis. RESULTS: There were 136 (41%) SLE patients presenting with at least one other AD. A total of 191 ADs were observed, of which the most frequent were autoimmune thyroid disease (AITD), antiphospholipid syndrome (APS) and Sjögren's syndrome (SS), registered in 60 (18%), 48 (14%) and 47 (14%) cases, respectively. Out of a total number of 1515 SLE patients with polyautoimmunity (1379 reported previously and 136 informed here) there were 77 (5.1%) cases with multiple autoimmune syndrome (i.e., two or more ADs in addition to SLE). Female gender, articular involvement, familial autoimmunity, anti-Ro positivity and patient's origin were risk factors for polyautoimmunity while the presence of anti-RNP antibodies was protective. Four clusters of ADs were found. The most hierarchical one was composed of AITD, APS, SS, and systemic sclerosis. CONCLUSION: Polyautoimmunity is frequent in SLE, and it is influenced by clinical and immunological features. These findings support that clinically different autoimmune phenotypes might share common susceptibility variants.

Successful treatment of relapsing autoimmune pancreatitis in primary Sjögren's syndrome with rituximab: report of a case and review of the literature.

Autoimmune pancreatitis (AIP) is a rare disorder often associated with multiple autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease and Sjögren's syndrome (SS). Although knowledge of AIP has grown over the last few years, little is certain about its cause and pathogenesis. Positive immunologic markers like antinuclear antibodies (ANA) or elevated serum levels of IgG4, systemic autoimmune disease association and positive response to oral steroid therapy strongly supports the idea of autoimmune mechanisms involved in the pathogenesis of AIP. We describe the first case reported on the literature of a patient with primary SS who developed relapsing AIP to steroids but responded successfully to Rituximab (RTX) therapy. New theories about the role of B-cells activity in SS and other autoimmune diseases has encourage the use of RTX, proving tolerance and efficacy especially in extra-glandular manifestations.

HLA class II association with autoimmune hepatitis in Latin America: a meta-analysis.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease to which different Human Leukocyte Antigens (HLA) have been associated, according to the ethnic/geographical group affected, age of presentation, prognosis, and serologic profile. OBJECTIVE: To identify common HLA class II alleles contributing to susceptibility to AIH in Latin American population. METHODS: The present study was held through a systematic review of the literature, followed by a meta-analysis of 694 cases and 1769 controls of all case-control studies that supplied enough information for odd ratio and 95% confidence interval calculation conducted to date in Latin America. RESULTS: The serological group DQ2 was found to be risk factor for AIH, while DR5 and DQ3 were found to be protective factors in this population. At the allelic level, DQB1*02, DQB1*0603, DRB1*0405, and DRB1*1301, were found to be risk factors, while DRB1*1302 and DQB1*0301 alleles were protective factors. The physicochemical similarities and differences of critical amino acids encoding the peptide binding groove at pockets P1, P4, and P6 of these HLA molecules, elucidates their influence in the development of disease. CONCLUSION: The current study strengthens the HLA component of AIH in Latin America and its relationship to other populations around the world.