Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Background and Objectives: Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Methods: Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. Results: 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Conclusion: Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Transmembrane Protein 187 (TMEM187) and Interleukin 1 Receptor Associated Kinase (IRAK1) gene polymorphism association with rheumatoid arthritis susceptibility in Egyptian patients.

Rheumatoid arthritis (RA) is a chronic auto-inflammatory disease of connective tissue with progressive joint damage and systemic disorders. RA is considered a multifactorial disease triggered by a genetic predisposition and environmental factors. Polymorphisms have been identified in the Xq28 locus as risk loci for RA. The aim of study was to assess the association between two polymorphisms in the Xq28 region containing Transmembrane Protein 187 (TMEM187) gene (rs13397) and interleukin1 receptor associated kinase (IRAK1) gene (rs1059703) with the disease susceptibility and activity in Egyptian RA patients. This study was conducted on 100 RA patients and 100 age and sex matched normal controls, together were recruited from the Rheumatology Department, Beni-Suef University Hospital. We detected TMEM187 (rs13397) and IRAK1 (rs1059703) gene polymorphisms using the real time PCR TaqMan allelic discrimination assays. We found that the frequency of the major genotypes (GG) of TMEM 187 gene was higher in RA group (54%) compared to controls (50%); while the minor genotypes (AA) was higher in the control group (22%) compared to the diseased one (18%), but such differences did not reach statistical significance (p=0.599). Regarding the IRAK1 gene, we revealed that the frequency of the major genotypes (AA) of the rs1059703 was slightly higher in RA group (48%) compared to controls (46%); while the minor genotypes (GG) was the same in both groups (26%). However, there was higher incidence of minor genotype in the TMEM187 and IRAK1 genes in males; with a statistical significance (p=0.004 and 0.015, respectively). We concluded that the major allele G of TMEM187(rs 13397) could be considered as a risk genetic allele for RA in Egyptian populations.

Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance.

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

High serum leptin and adiponectin levels as biomarkers of disease progression in Egyptian patients with active systemic lupus erythematosus.

Objectives: Leptin and adiponectin are adipose-derived immune modulators (adipokines) that may contribute to SLE pathology and symptoms. This study aimed to evaluate the associations of serum adiponectin and leptin with clinical manifestations and disease activity in SLE patients. Methods: This is a case control study, where 70 SLE patients and 50 age- and sex-matched healthy controls were enrolled from the Rheumatology and Rehabilitation Department of Beni-Suef University Hospital from June 2020 till April 2022. The SLE disease activity index (SLEDAI) and Systemic Lupus International Collaborative clinics/America Collage of Rheumatology damage index were used to assess disease severity. Laboratory parameters including erythrocyte sedimentation rate (ESR) and serum concentrations of antinuclear antibody (ANA), anti-double stranded DNA, complement 3 and 4, lipids, and C-reactive protein (CRP) were measured and compared between SLE and control groups. Serum adiponectin and leptin were also measured by enzyme-linked immunosorbent assays (ELISA). Results: Compared to healthy controls, SLE patients exhibited significantly greater serum leptin (21.1 vs 3.9 ng/mL, p < 0.001) and adiponectin (18.1 vs 4.8 ng/mL, p < 0.001), and both values were positively correlated with SLEDAI scores (p = 0.048 and 0.042). Higher serum leptin was significantly associated with lupus nephritis (LN) (p = 0.048) as well as greater body mass index (p = 0.010), ESR (p = 0.002), serum CRP (p = 0.003), total cholesterol (p = 0.013), and uric acid (p = 0.002), while higher adiponectin was significantly associated with LN (p = 0.046). Conclusion: Serum leptin and adiponectin levels are associated with the clinical and pathological manifestations of SLE, suggesting direct involvement in disease progression and utility as diagnostic biomarkers and therapeutic targets.

Comorbidities among Egyptian systemic lupus erythematosus: The COMOSLE-EGYPT study.

OBJECTIVE: To study the prevalence and impact of comorbidities among a cohort of patients with systemic lupus erythematosus (SLE). METHODS: This study is retrospective, multicenter including 902 Egyptian patients with SLE. Medical records were reviewed for demographic data, clinical characteristics, routine laboratory findings, immunological profile, and medications. Moreover, SLE Disease Activity Index (SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College Rheumatology Damage Index scores were calculated. RESULTS: Comorbidities were found in 75.5% of the studied group with hypertension and dyslipidemia as the most frequent comorbidities (43.1% and 40.1%, respectively), followed by sicca features, avascular necrosis, diabetes, osteoporosis and renal failure (11.5%,9%, 9%,8.9%, and 7.1%, respectively). Multivariate regression model showed statistically significant relation between the presence of comorbid condition and each of age (P = 0.006), disease duration (P = 0.041), SLEDAI at onset (P < 0.001), cyclophosphamide intake (P = 0.001), and cumulative pulse intravenous methylprednisone (P < 0.001). Also, when adjusted to age and sex, those with multiple comorbid conditions had 18.5 increased odds of mortality compared to those without comorbidities (odds ratio (OR), 95% confidence interval (CI) = 18.5 (6.65-51.69)]. CONCLUSION: Patients with SLE suffer from several comorbidities, with an increasing risk with age, longer disease duration, higher SLEDAI at onset, cyclophosphamide intake and cumulative pulse intravenous methylprednisone. Risk of mortality is exponentiated with multiple comorbidities.

The Impact of Micro RNA-320a Serum Level on Severity of Symptoms and Cerebral Processing of Pain in Patients with Fibromyalgia.

OBJECTIVES: The aim of this work was to explore the expression of miR-320a level in fibromyalgia patients in comparison to healthy controls, and to clarify its impact on the severity of symptoms and the cerebral processing of pain assessed by middle latency somatosensory evoked potentials (SSEPs). DESIGN: Case-control study. SETTING: Rheumatology and Neurology outpatient clinics. SUBJECTS: Seventy-four fibromyalgia patients and seventy-four normal healthy controls. METHODS: The included patients were subjected to detailed history taking, assessment of severity of fibromyalgia symptoms using the Fibromyalgia Impact Questionnaire Revised (FIQR), assessment of pain intensity using the Neuropathic Pain Symptom Inventory (NPSI), measurement of the serum level of miR-320a in addition to of measurement peak latencies and amplitudes of middle latency SSEPs. RESULTS: Fibromyalgia patients had significantly higher micro-RNA-320a levels (0.907 ± 0.022) in comparison to controls (0.874 ± 0.015) (P-value < .001). The mean values of micro-RNA-320a levels were significantly higher in fibromyalgia patients with insomnia, chronic fatigue syndrome, persistent depressive disorder, and primary headache disorder than those without (P-value = .024, <.001, .006, .036 respectively). There were statistically significant positive correlations between micro-RNA-320a levels, and disease duration, FIQR, and NPSI total scores (P-value <0.001, 0.003, 0.002 respectively). There were no statistically significant correlations between micro-RNA-320a levels and middle latency SSEPs. DISCUSSION: Micro-RNA-320a level is significantly upregulated in fibromyalgia patient. It has a crucial impact on the severity of symptoms but not related to the cerebral processing of pain.

Circulating miR-146a -5p in Egyptian patients with Rheumatoid Arthritis.

We indented to evaluate of the role miRNA-146a-5p expression level as a possible biomarker associated with the incidence of rheumatoid arthritis and the detection of its relevance with different disease parameters. The study included 60 clinically diagnosed RA patients fulfilling 2010 American College of Rheumatology / European League Against Rheumatism (ACR/EULAR) classification criteria for Rheumatoid Arthritis and 45 age and sex matched control subjects. Disease activity was assessed by Disease Activity Score 28 (DAS28). The expression levels of miR-146a in whole blood was measured using reverse transcriptase quantitative real time polymerase chain reaction (RT-PCR). There median expression level of miRNA-146a-5p was significantly higher in RA patients compared with the control group (P = 0.036). MiR-146a expression level was positively correlated with individual activity markers, including erythrocyte sedimentation rate (ESR) (P = 0.04), visual analogue scale (VAS) (P = 0.047) and Modified Health Assessment Questionnaire (MHAQ) (P = 0.050). A lower expression level of miRNA-146a-5p was detected in RA patients on antimalarial drugs as compared to patients whose treatment protocol did not include antimalarial drugs (P = 0.016). In conclusion, data of this study suggested a possible association between miRNA 146a-5p expression level and the incidence of RA in Egyptian patients.

Tumour necrosis factor gene polymorphisms in Egyptian patients with rheumatoid arthritis and their relation to disease activity and severity.

AIM OF THE STUDY: The present case control study was conducted to assess the association of LTA 252 A>G, TNF-α 308 G>A, and TNF-α 1031 T>C gene polymorphisms with rheumatoid arthritis (RA), and their involvement in disease activity and severity. MATERIAL AND METHODS: A total of 70 Egyptians, including 35 RA patients and 35 healthy control individuals, were included in the study. The RA patients comprised 34 females and one male. Cases with RA were diagnosed by a rheumatologist and fulfilled the 2010 ACR/EULAR criteria. Modified disease activity score (DAS28) was used to assess disease activity. Van Der Heijde-modified Sharp score (vdHSS) was used to assess radiological changes for assessment of disease severity. PCR-RFLP was used to detect the association of LTA 252 A>G, TNF-α 308 G>A, and TNF-α 1031 T>C gene polymorphisms with RA. RESULTS: TNF-α 308 G allele and TNF-α 308 GG genotype were significantly higher in RA patients compared to healthy control subjects (p = 0.04 and p = 0.001, respectively). TNF-α 308 G allele and GG genotype were significantly higher in the RA non-remission group compared to the remission group (p = 0.008, p < 0.001). Patients with the TNF-α 308 AG genotype had higher mean of Sharp score compared to the patients with the GG and AA genotypes (p = 0.007). There was no significant association between LTA 252 A>G and TNF-α 1031 T>C gene polymorphisms and RA. CONCLUSIONS: Our results suggest that TNF-α 308 G/A gene polymorphism is genetically associated with RA and involved in disease activity and severity in Egyptian patients.