John Londoño

Heat shock protein 70 gene polymorphisms in Mexican patients with spondyloarthropathies

Objective: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, χ2, Fishers exact test, and Woolfs method for odds ratio (OR). Results: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC<0.05, OR=4.3), as well as in the different clinical subgroups (pC<0.05, OR=4.2 for AS; pC<0.05, OR=4.4 for uSpA; and pC<0.05, OR=4.1 for ReA). This frequency remained significantly increased when the patients with B27 negative SpA were analysed. On the other hand, HSP70-hom locus analysis showed significantly increased frequency of A allele in the whole group of SpA (pC<0.05, OR=3.4), as well as in the groups with AS (pC<0.05, OR=5.6) and with uSpA (pC<0.05, OR=3.1), when compared with healthy controls. In this case, also, the genotype A/A was increased in the whole group of SpA (pC<0.05, OR=4.5), as well as in patients with AS (pC<0.05, OR=6.4) and with uSpA (pC<0.05, OR=3.7). When the patients with B27 negative SpA were analysed the frequencies of HSP70-hom A allele and A/A genotype remained significantly increased in the whole group of SpA (pC<0.05, OR=3.2 for the A allele and pC<0.05, OR=4.2 for the A/A genotype) and in the uSpA subgroup (pC<0.05, OR=3.8 for the A allele and pC<0.05, OR=4.3 for the A/A genotype). Conclusion: In addition to the association of SpA with HLA-B27, there is a significant association of HSP70-2 and HSP70-hom alleles with SpA in Mexicans. This association seems to be independent of the susceptibility conferred by HLA-B27 in the group of patients with uSpA.

Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients

Objective: To investigate the role of HLA-B and HLA-DR genes as contributors to genetic susceptibility and clinical expression of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 172 patients with SpA (undifferentiated SpA 83, ankylosing spondylitis (AS) 64, and reactive arthritis 25) and 99 healthy controls. The HLA-B and HLA-DR alleles were detected by the polymerase chain reaction with sequence-specific primers technique. Patient assessment included demographic data, diagnostic categories, and disease patterns. Statistical methods included the Mantel-Haenzel χ2 test, Fishers exact test, and Woolf method for odds ratio (OR). Differences of continuous variables between HLA allele groups were calculated by Students t test. Results: Increased frequencies of HLA-B27 (pCh10−3, OR=28.7), HLA-DR1 (pC=0.045, OR=2.77), and HLA-B15 (p=0.034, pC=NS, OR=2.04) alleles in the whole group were found. HLA-B27 strength of association (OR) was 41.4 in AS; 20.9 in undifferentiated SpA; 27.2 in reactive arthritis. HLA-DR1 and HLA-B15 were increased in undifferentiated SpA (pC=0.045, OR=2.98 and p=0.004, pC=NS, OR=2.75). By analysing 58 HLA-B27 negative patients it was found that HLA-B15 and HLA-DR1 associations with SpA were independent of HLA-B27; increased frequencies of HLA-B15 were found in the whole SpA group and in patients with undifferentiated SpA (pC=0.03, OR=3.09 and pCh0.01, OR=3.77) and of HLA-DR1 in the latter (p=0.04, pC=NS, OR=3.15). HLA-B27 positive patients were younger than HLA-B27 negative patients at onset (p=0.03), but HLA-DR1 positive patients were older than HLA-DR1 negative patients (p=0.03). Bath indices for disease activity and functioning were higher in HLA-B27 positive patients (p=0.006 and p=0.004 v HLA-B27 negative patients). In contrast, neither HLA-DR1 nor HLA-B15 influenced these indices. Conclusion: Apart from HLA-B27, there is a significant association of HLA-DR1 and HLA-B15 with SpA in Mexicans which is independent of B27. HLA-B27 is associated with younger age at onset and increased disease severity and HLA-DR1 with older age at onset. The strength of HLA-B15, HLA-B27, and HLA-DR1 associations varied in different forms of SpA.

Low frequency of anticyclic citrullinated peptide antibodies in psoriatic arthritis but not in cutaneous psoriasis.

Background:Anticyclic citrullinated peptide (anti-CCP) antibodies are highly specific for the diagnosis of rheumatoid arthritis (RA). The clinical distinction between RA and psoriatic arthritis (PsA) is often difficult to establish; therefore, the presence of rheumatoid factor (RF) and anti-CCP antibodies could be useful. Seven percent to 40% of patients with longstanding psoriasis will develop PsA at some point. Therefore, it is important to study the positivity of these antibodies in these two interrelated populations. Objective:The aim of this study was to determine the seropositivity of anti-CCP antibodies in patients with psoriasis and PsA and to compare it with that seen in patients with other inflammatory, noninflammatory (osteoarthritis) arthritides and healthy controls. Patients and Methods:Serum anti-CCP antibodies were measured in 106 patients with cutaneous psoriasis, 72 patients with PsA, 41 healthy controls (HC), 41 patients with undifferentiated or early inflammatory arthritis (UA), and 41 patients with RA and 41 with osteoarthritis using a commercial second-generation enzyme-linked immunosorbent assay. We considered a positive result to be >20 UI/mL, as recommended by the manufacturer. Results:Of 106 patients with PsA, 55 were women and 51 men. The mean age was 42.87 ± 17.71 years and the mean disease duration was 5.3 ± 2.10 years. Anti-CCP antibodies were not present in patients with psoriasis without arthritis. In contrast, 7 of 72 (9.72%) patients with PsA were positive for anti-CCP antibodies with a median titer of 7.16 units. Only one patient with PsA was positive for RF. Most of these patients were female with polyarticular joint involvement. Distal interphalangeal involvement was present in 4 and 2 had dactylitis. We found clear differences when we compared patients with PsA with patients with psoriasis (P = 0.001). Of the 43 patients with UA studies, 4 initially exhibited a low titer positive anti-CCP antibody, and at follow up, another patient developed anti-CCP antibodies and later developed RA. None of the patients with UA developed PsA at 5-year follow up. Thirty-two of the 41 patients had a positive anti-CCP antibody and the mean ± standard deviation of the anti-CCP units was 80.61 ± 55.5.2. Six of the 41 (14.6%) patients with osteoarthritis studied had positive anti-CCP with a mean titer of 7.388. None of the healthy controls exhibited positively for anti-CCP antibodies. Conclusion:Anti-CCP antibodies may be found in patients with PsA and not in our patients with only cutaneous psoriasis. These antibodies may also be found in some patients with osteoarthritis and rarely in patients with UA; such patients will be of interest to follow prospectively.

Serum monocyte chemotactic protein-1 concentrations distinguish patients with ankylosing spondylitis from patients with mechanical low back pain.

Objectives This study aimed to identify potential blood-derived biomarkers distinguishing patients with ankylosing spondylitis from those with mechanical low back pain. Methods Serum and synovial fluid samples from our cohorts were assayed by using enzyme-linked immunosorbent assay for the following inflammatory biomarkers: interleukin (IL)-1&agr;, IL-6, IL-8, IL-17, IL-23, monocyte chemotactic protein (MCP)-1, macrophage inflammatory proteins (MIP)-1&agr;, MIP-1&bgr;, tumor necrosis factor-&agr; (TNF-&agr;), interferon-&agr; (IFN-&agr;), IFN-&bgr;, metalloproteinase (MMP-3), and bone morphogenetic protein 7 (BMP-7). Results After screening, a panel of serum and synovial fluid samples with a series of potential biomarkers, cytokines including IL-6, IL-8, MMP-3, and MCP-1 were selected for additional testing because they exhibited higher concentrations than paired serum samples in the synovial fluid. Sera obtained from 50 patients with ankylosing spondylitis and 27 patients with mechanical low back pain were measured for these biomarkers. Conclusions The MCP-1 serum was identified as a biomarker candidate, distinguishing ankylosing spondylitis from mechanical low back pain with a sensitivity of 96% and a specificity of 83.3%.

Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early Rheumatoid Arthritis: A Cross-Sectional Study

BACKGROUND Recent consensus emphasizes the importance of studying individuals at risk for rheumatoid arthritis (pre-RA) and those with early RA (eRA). Periodontal tissues have been recently evaluated, but these studies are limited. To evaluate the periodontal condition, immunoglobulin (Ig)G subclasses against Porphyromonas gingivalis in individuals with pre-RA and eRA were compared with controls to establish an association between periodontal infection markers and rheumatic activity. METHODS Rheumatologic and periodontal condition was evaluated in 119 individuals with pre-RA, 48 patients with eRA, and matched controls. P. gingivalis IgG1 and IgG2 were analyzed. C-reactive protein, erythrocyte sedimentation rate (ESR), rheumatoid factor, anticitrullinated protein antibodies (ACPAs), and RA activity were measured. The groups were compared with McNemar test and paired t-test. Conditional logistic regression was performed for pre-RA confounders, and χ(2) test was used to evaluate periodontal variables and RA activity indices. RESULTS Pre-RA individuals showed significantly higher levels of plaque index (P = 0.01) and bleeding on probing (P = 0.03) and higher severity of periodontal disease (P = 0.02). Periodontitis was associated with pre-RA (odds ratio, 3.39; 95% confidence interval, 1.64 to 7.01) but not with eRA. In pre-RA, P. gingivalis-specific IgG2 was associated with ACPAs (P = 0.049) and disease severity visual analog scale (P = 0.03). In eRA, IgG2 against P. gingivalis was associated with ESR (P = 0.046) and ACPAs (P = 0.04). P. gingivalis was associated with ACPAs (P = 0.04). CONCLUSIONS This study shows that individuals with pre-RA have significant inflammatory periodontal involvement. There was a significant association between IgG against P. gingivalis and ACPAs in pre-RA and markers of RA activity in individuals with eRA.

Epidemiology of Spondyloarthritis in Colombia

There are no formal statistics about the incidence, prevalence or demographics of patients with spondyloarthropathies (SpAs) in Colombia. However, information from a few studies provides a preliminary snapshot of SpAs in the country. In this article, the authors review what has been published; document what their group is doing and outline what they still need to do in the future. The analysis suggests that although information on SpA in Colombia is limited, it is known that the diagnostic entities of SpA are different than those reported at other latitudes. Thus, it is important to improve and expand the current database of SpA, particularly undifferentiated SpA, not only in Colombia but in all of Latin America.

Biomarcadores en espondiloartropatías

Among rheumatic diseases and specifically spondyloarthropathies (SpA), the study of biomarkers, defined as molecules that reflect either biologic or specific pathological process, is an important and necessary area in basic and clinical research, being a consequence or the response of an intervention. Other markers provide information about the pathogenesis of this disease. Recently, HLA-B27 has been used as diagnostic criteria to detect SpA. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) are clinical scores used to assess disease activity. A new activity index, Ankylosing Spondylitis Disease Activity Score (ASDAS) considers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as biomarkers. This review describes the state of the art of research on SpA biomarkers. There are promising new candidates as biomarkers such as metallopro-teinase 3, Type II collagen neoepitopes (C2C and C1-2C), C-propeptide of Type II collagen (CPII), aggrecan 846 epitope, macrophage colony stimulating factor, serum amyloid A protein and interleukin-6, among others.

Eficácia terapêutica e segurança de metotrexato + leflunomida em pacientes colombianos com artrite reumatoide ativa refratária ao tratamento convencional

INTRODUCTION: The combination of methotrexate (MTX) + leflunomide (LFN) has been shown to be effective in the treatment of RA. Its safety has been questioned. OBJECTIVE: To evaluate the effectiveness and safety of the combination of MTX + LFN in patients with active RA. METHODS: This was a 24-week multicenter study, which included 88 patients with active disease despite consistent treatment with methotrexate and prednisolone. RESULTS: We included 78 women (88%) and 10 men. The age was 51.3 ± 12.4 years, and the evolution of disease was 8 ± 6.8 years. Patients had active disease, which was indicated by a median of IQR of 10.0 (7.0-13.0) for swollen and of 14.0 (18.0-10.0) for tender joints for the whole group. The ACR responses achieved at week 24 were: ACR20: 76.0%; ACR50: 67.1%; ACR70: 23.9%. There was improvement in the activity of disease: DAS-28 score: 5.8 ± 1.2 at baseline vs. 3.8 ± 1.6 at week 24 (P = 0.000). The most significant adverse event was elevation of transaminases in eight patients (26%). Eight patients were withdrawn due to adverse events: four due to the elevation of transaminases, and one each due to diabetes insipidus, rash, diabetes mellitus and osteomuscular pain. CONCLUSION: The combination of MTX + LFN is effective for treating RA in patients for whom conventional treatment has failed. Strict medical and laboratory control is to be enforced for safety.

Associations of the Levels of C4d-bearing Reticulocytes and High-avidity Anti-dsDNA Antibodies with Disease Activity in Systemic Lupus Erythematosus

Objective. There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales. Methods. All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured. Results. Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains. Conclusion. R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.

Risk factors and prevalence of osteoporosis in premenopausal women from poor economic backgrounds in Colombia

Introduction The prevalence of osteoporosis in premenopausal women along with associated risk factors has not been well elucidated. Recent studies have shown that poverty is a risk factor for osteoporosis. Objective To determine the prevalence of osteoporosis and its risk factors in a group of premenopausal women of poor economic background in Colombia. Materials and methods The study comprised 1483 women between 35 and 53 years of age with at least one risk factor for osteoporosis. Demographic characteristics, reproductive factors, comorbidities, and risk factors for osteoporosis were evaluated. Lumbar vertebrae (L2–L4) and the femur neck were assessed using dual-energy X-ray absorptiometry. Results Of the 1483 patients, 1443 (97.3%) had at least one risk factor for osteoporosis and 40 (2.7%) had no risk factors. Patients with one risk factor were referred to have a dual-energy X-ray absorptiometry scan, which 795 women completed. Osteopenia was found in 30.5% and osteoporosis in 4.8% of these women. The majority of these women were homemakers, and 18.5% of the patients with osteoporosis were also illiterate (P < 0.001). The risk factors identified in this population were: hypothyroidism (odds ratio [OR] = 5.19, 95% confience interval [CI]:1.6–16), age over 45 years old (OR = 1.13, 95% CI: 1.0–1.2), a history of malnutrition or low birth weight (OR = 2.35, 95% CI: 1.0–5.2), or early-onset menopause (OR = 3.4, 95% CI: 1.6–7.2). Conclusion Premenopausal Colombian women from impoverished areas showed increased rates of osteopenia and osteoporosis compared with the data described in the current literature. Hypothyroidism was an outstanding risk factor in Colombian premenopausal women with osteoporosis. This shows the influence of poverty and other risk factors on the onset of osteoporosis in women aged 35–53 years.