Exploring the Correlation between Interleukin-17A Promoter Polymorphism at its -197 G/A and Rheumatoid Arthritis: Impact on Disease Severity and Activity.

T helper 17 (Th17) cells have been reported to be the most powerful factor in autoimmune disorder pathogenesis, which points to the Th17 master cytokine, interleukin (IL)-17A, as the crucial mediator. We aimed to determine the impact of IL-17A polymorphism in the -197 G/A promoter region on level of IL-17 and intensity of rheumatoid arthritis (RA) disease symptoms. This case-control study was conducted at the Department of Clinical Rheumatology of Aswan university Hospital and included 35 people suffering RA and 30 volunteer controls, matched for age and sex. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), serum IL-17, and C-reactive protein (CRP) were measured in the RA patient group. Restriction fragment length polymorphism (RFLP) was conducted by polymerase chain reaction (PCR) amplicon obtained by IL-17A -197 G /A primers. Of the 35 RA patients, RF was positive in 33 (94.29%) and anti-CCP antibodies in 25 (71.43%), CRP in 31 (88.57%). Of the 35 RA patients, 5 (14.29%) patients carried the G/G genotype, 18 (51.43%) G/A and 12 (34.29%) A/A. IL-17 serum level was significantly greater in the more active RA (DAS28 >5.1) group than the less active (DAS28 ≤5.1) group. Of the RA patients carrying wild type G/G genotype, 60% had more active disease (DAS 28> 5.1), as compared to those with lower activity (DAS 28 ≤5.1), 40% carried the wild type G/G genotype. In conclusion, the study findings imply that IL-17A gene polymorphism is connected to RA clinical severity rather than with RA susceptibility.

Study the Relationship of MDCT Staging in Disease Extent with the Systemic Sclerosis Disease Parameters / Estudiar la relación de la estadificación de la TCMD en la extensión de la enfermedad con los parámetros de la enfermedad de esclerosis sistémica

Background and objectives: The highest incidence of death in systemic sclerosis due to pulmonary disease raises the need for early detection and treatment. The study aim is the assessment of interstitial pulmonary disease by Multi Detector High Resolution CT (MDCT) and finds its relationship with the other disease parameters and the Pulmonary Function tests (PFT). Patients and methods: A prospective cross-sectional study was performed in Assiut University Hospitals from May 2018 to January 2020 and included 62 consecutive SSc female patients. Demographic, clinical, Laboratory, PFT and MDCT assessment were conducted for all participants. Results: The coarseness of fibrosis was 8.32 (range 0.0–17), the average proportion of ground-glass opacification was 28.3% (range, 0.0%–75%). Honey-comb pattern was seen in (52.5%). Mean Extent of disease was 46.25±3.7 (range 5–81). Restrictive deficit found in 42 patients. Significant relation was found between the extent of disease and the percentage predicted FVC (r=0.373, p 0.018) and FEV1/FVC (r=0.593, p 0.000) and coarseness of fibrosis and proportion of ground glass opacification correlated inversely with VC (r=−0.385, p=0.014, r=−0.376, p=0.017 respectively), Rayanud's phenomena, modified Rodnan Skin Score and Medsger's general are positively correlated with MDCT disease extent. Conclusion: Scoring of systemic sclerosis (SSc) related interstitial lung disease (SSc-ILD) could be applicable as one of the important tools for disease assessment.(AU)

Justificación y objetivos: La mayor incidencia de muerte en la esclerosis sistémica por enfermedad pulmonar plantea la necesidad de una detección y un tratamiento precoces. El objetivo del estudio es la evaluación de la enfermedad pulmonar intersticial mediante TC de alta resolución multidetector (TCMD) y encuentra su relación con otros parámetros de la enfermedad y con pruebas de funcionamiento pulmonar (PFP). Pacientes y métodos: Se realizó un estudio transversal prospectivo en los hospitales universitarios de Assiut desde mayo de 2018 hasta enero de 2020 que incluyó 62 pacientes femeninas de esclerosis sistémica consecutivas. Se realizaron evaluaciones demográficas, clínicas, de laboratorio, PFP y TCMD para todos los participantes. Resultados: La aspereza de la fibrosis fue de 8,32 (rango 0,0-17) y la proporción promedio de opacificación en vidrio esmerilado fue del 28,3% (rango 0,0-75%). Se observó un patrón de panal de miel en el 52,5%. La extensión media de la enfermedad fue de 46,25±3,7 (rango 5-81). Se encontró déficit restrictivo en 42 pacientes. Se encontró una relación significativa entre la extensión de la enfermedad y el porcentaje predicho de capacidad vital forzada (CVF) (r=0,373, p=0,018) y FEV1/CVF (r=0,593, p=0,000) y la aspereza de la fibrosis y la proporción de opacificación en vidrio esmerilado se correlacionaron inversamente con la capacidad vital (r=−0,385, p=0,014; r=−0,376, p=0,017, respectivamente), los fenómenos de Rayanud, m Rodnan Skin Score y Medsger general se correlacionan positivamente con la extensión de la enfermedad por TCMD. Conclusión: La puntuación de la enfermedad pulmonar intersticial relacionada con la esclerosis sistémica podría ser aplicable como una de las herramientas importantes para la evaluación de la enfermedad.(AU)

Study the Relationship of MDCT Staging in Disease Extent with the Systemic Sclerosis Disease Parameters.

BACKGROUND AND OBJECTIVES: The highest incidence of death in systemic sclerosis due to pulmonary disease raises the need for early detection and treatment. The study aim is the assessment of interstitial pulmonary disease by Multi Detector High Resolution CT (MDCT) and finds its relationship with the other disease parameters and the Pulmonary Function tests (PFT). PATIENTS AND METHODS: A prospective cross-sectional study was performed in Assiut University Hospitals from May 2018 to January 2020 and included 62 consecutive SSc female patients. Demographic, clinical, Laboratory, PFT and MDCT assessment were conducted for all participants. RESULTS: The coarseness of fibrosis was 8.32 (range 0.0-17), the average proportion of ground-glass opacification was 28.3% (range, 0.0%-75%). Honey-comb pattern was seen in (52.5%). Mean Extent of disease was 46.25±3.7 (range 5-81). Restrictive deficit found in 42 patients. Significant relation was found between the extent of disease and the percentage predicted FVC (r=0.373, p 0.018) and FEV1/FVC (r=0.593, p 0.000) and coarseness of fibrosis and proportion of ground glass opacification correlated inversely with VC (r=-0.385, p=0.014, r=-0.376, p=0.017 respectively), Rayanud's phenomena, modified Rodnan Skin Score and Medsger's general are positively correlated with MDCT disease extent. CONCLUSION: Scoring of systemic sclerosis (SSc) related interstitial lung disease (SSc-ILD) could be applicable as one of the important tools for disease assessment.

Study the Relationship of MDCT Staging in Disease Extent with the Systemic Sclerosis Disease Parameters.

BACKGROUND AND OBJECTIVES: The highest incidence of death in systemic sclerosis due to pulmonary disease raises the need for early detection and treatment. The study aim is the assessment of interstitial pulmonary disease by Multi Detector High Resolution CT (MDCT) and finds its relationship with the other disease parameters and the Pulmonary Function tests (PFT). PATIENTS AND METHODS: A prospective cross-sectional study was performed in Assiut University Hospitals from May 2018 to January 2020 and included 62 consecutive SSc female patients. Demographic, clinical, Laboratory, PFT and MDCT assessment were conducted for all participants. RESULTS: The coarseness of fibrosis was 8.32 (range 0.0-17), the average proportion of ground-glass opacification was 28.3% (range, 0.0%-75%). Honey-comb pattern was seen in (52.5%). Mean Extent of disease was 46.25±3.7 (range 5-81). Restrictive deficit found in 42 patients. Significant relation was found between the extent of disease and the percentage predicted FVC (r=0.373, p 0.018) and FEV1/FVC (r=0.593, p 0.000) and coarseness of fibrosis and proportion of ground glass opacification correlated inversely with VC (r=-0.385, p=0.014, r=-0.376, p=0.017 respectively), Rayanud's phenomena, modified Rodnan Skin Score and Medsger's general are positively correlated with MDCT disease extent. CONCLUSION: Scoring of systemic sclerosis (SSc) related interstitial lung disease (SSc-ILD) could be applicable as one of the important tools for disease assessment.

Predictors of Cardiovascular Affection in Patients with Active Rheumatoid Arthritis: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: This is a secondary analysis of a randomized controlled trial that aimed to assess subclinical atherosclerosis in patients with rheumatoid arthritis (RA) by measuring carotid artery intima-media thickness (CIMT) and correlating it with disease activity and inflammatory markers (including levels of matrix metalloproteinase-3(MMP-3) and matrix metalloproteinase-9 (MMP-9)) and to detect the effectiveness of agents that inhibit matrix metalloproteinases (MMPs) as doxycycline in RA therapy. METHODS: One hundred and sixty RA patients were assigned in a randomized clinical trial (clinicaltrial. gov NCT03194204). Disease activity score 28(DAS28), laboratory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MMP-3, and MMP-9 were evaluated and mean CIMT was measured. Subjects were allocated randomly into one of two treatment arms, either methotrexate (MTX) alone or MTX with doxycycline 200mg per day orally. Follow up ESR, CRP, DAS28, MMP-3, and MMP-9 levels were re-evaluated after 3 months. RESULTS: There were positive significant correlations between CIMT and disease duration (r = 0.461, p = 0.001), age (r=0.459, p= 0.001), DAS28 score (r= 0.547, p = 0.001), ESR (r =0.413, p = 0.001), CRP (r = 0.281, p = 0.001), MMP-3 (r = 0.476, p = 0.001), and MMP-9 (r = 0.593, p =0.001). Patients treated with MTX and doxycycline showed lower levels of DAS28, ESR, CRP, MMP-3, and MMP-9 and this was statistically significant. CONCLUSION: CIMT seems to be the ultimate method to screen for subclinical atherosclerosis in RA patients. MMP-3 and 9 play a key role in both RA synovitis and cardiovascular changes, making them important therapeutic targets, especially with safe and cost-effective agents like doxycycline. This clinical trial was carried out in Assiut University Hospital (AUH), Assiut, Egypt (Clinical Trial Registration No. clinicaltrial.gov NCT03194204).

Is There a Feasible Link between Vitamin D Receptor Genotypic and Allelic Frequencies with Analytical Biomarkers of Rheumatoid Arthritis Disease?

Rheumatoid arthritis (RA) is one of the most widespread autoimmune disorders and it has a genetic background with a variety of genes affecting the degradation of the immune system. Along these lines, we assessed the relationship between the BsmI, and FokI VDR polymorphisms and inflammable records identified with infections activity. Such as interleukins (IL-6, IL-8), hypoxia inducible factor-alpha (HIF-α), soluble receptor of advanced glycation end product (sRAGE), oxidized low-density lipoprotein cholesterol (oxLDL), neutrophil gelatinase-associated lipocalin (NGAL) and procollagen N-propeptide of type III collagen (P3NP) and the allelic frequencies of BsmI VDR rs1544410 and FokI VDR rs2228570 polymorphism on the RA. Total of 131 subjects [70 RA patients and 61 age and sex matched apparently healthy controls (HC)] were monitored for inflammatory biomarkers using ELISA. All patients were screened for the BsmI and FokI using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The all biomarkers were significantly higher in RA patients in comparison with HC. There were positive correlations between NGAL, oxLDL and s-RAGE, oxLDL. On BsmI, 'GG' and 'AG' genotypes were significantly associated with high RA activity as well as the frequency of genotypes 'AG & GG" were higher in high activity RA as compared to low RA activity. However on FokI, was observed that in high activity patients the frequency of 'CC' & 'CT' was more prevalent as compared to low activity ones. These outcomes support the immunoregulatory role of vitamin D which is associated with several inflammatory diseases, signifying a credible anti-inflammatory role in perturbation of the RA.