Growth arrest-specific protein 6 as a marker of nephritis in systemic sclerosis and juvenile systemic lupus erythematosus patients.

Background: Renal impairments commonly occur as a complication of autoimmune connective tissue diseases (CTDs). Therefore, early nephritis prediction is vital for patient outcomes. Growth Arrest-Specific Protein 6 (GAS6) was found to be upregulated in many types of inflammatory renal disease, including diabetic nephropathy.Aim: To evaluate GAS6 as a predictor of renal impairment in adults with systemic sclerosis (SSc) and children with systemic lupus Erythematosus (SLE).Methods: The study included 60 patients with SSc and 40 children with SLE. The serum level of GAS6 was measured using the ELISA technique. In adults with SSc, total proteins in 24-h urine concentration of >300 mg/24 h indicated renal inflammation, while in children with SLE, nephritis was diagnosed by abnormal renal pathology.Results: In SSc patients, GAS6 significantly increased in patients with proteinuria. GAS6 is an independent predictor of nephritis with an odds ratio (OR) of 1.06 and a 95% confidence interval (CI) of 1.0-1.1. at cutoff 12.2 ng/mL GAS6 predicted proteinuria with sensitivity 86.7% (95% CI: 59.5% to 98.3%), specificity 57.8% (95% CI: 42.1% to 72.3%), positive predictive value 40.6% (95% CI: 31.5% to 50.4%), negative predictive value 92.9% (95% CI: 77.7% to 97.73%), and accuracy 65.0% (95% CI: 51.6% to 76.9%). In SLE patients, Serum GAS6 did not differ significantly between children with and without lupus nephritis.Conclusion: GAS6 is an independent predictor of nephritis in patients with SSc. However, there is no association between GAS6 and nephritis in juvenile patients with SLE.

HLA-DRB1, IRF5, and CD28 gene polymorphisms in Egyptian patients with rheumatoid arthritis: susceptibility and disease activity.

This study was established to assess the effects of IRF5 rs10488631 and CD28 rs1980422 single-nucleotide polymorphisms (SNPs) and HLA-DRB1 shared epitope (SE) allele on the prognosis and disease activity of rheumatoid arthritis (RA) patients. A total of 150 RA patients and 150 healthy controls were genotyped for the selected SNPs by real-time PCR. HLA-DRB1 SE was determined using LAB Type SSO Class II DRB1 typing. Our results suggest that HLA-DRB1, CD28, and IRF5 significantly discriminated (p < 0.001) RA patients and healthy controls (OR of single HLA-DRB1 SE allele = 2.431, CI = 1.467-4.027, OR of two SE alleles = 11.152, CI = 2.479-50.159), (OR of CD28 risk allele C = 2.794, 95% CI = 1.973-3.956) and (OR of IRF5 risk allele C = 4.925, CI = 3.26-7.439). Rheumatoid factor (RF) seropositivity was associated with HLA-DRB1 SE (p < 0.001) and IRF5 risk allele (p < 0.001). ACPA was significantly associated only with IRF5 risk allele (p < 0.001). A better response to methotrexate therapy was found in HLA-DRB1 SE non-carriers, and CD28 TT patients. This study demonstrated associations of HLA-DRB1 SE, CD28, and IRF5 with the risk of RA. HLA-DRB1 SE and CD28 rs1980422 can be used as predictors of methotrexate therapy response.

Impact of intensive training on mental health, the experience of Port Said, Egypt.

BACKGROUND: Mental disorder is extremely common globally and integration of mental health in primary health services represents a critical gap especially in low- and middle-income Countries like Egypt. The World Health Organization has repeatedly called for effective training and support of primary care providers in the identification and treatment of mental health problems over the last decades. METHODS: This paper aimed to evaluate attitudes and knowledge of health care providers toward mentally ill patients and measure knowledge and retention of training messages over time. A 3-day mental health training workshop for nurses of public health facilities in the Governorate of Port Said was organized. Pre-training and post-training questionnaires (immediately after the workshop and 3 months later) were used. Significance of gain in scores was examined between baseline and following cross sectional rounds. RESULTS: The 73 participants in the study revealed a statistically significant improvement in knowledge and attitude toward mental health from the baseline (pre-training), from a general mean score for desirable answers of 10.5 (± 1.2) to 21.2 (± 0.6). However, results slightly declined three months after from the workshop (18.5 (± 0.6)). CONCLUSIONS: Intensive short-term training on mental illness could be instrumental in improving knowledge and attitudes in countries like Egypt with extensive needs in terms of quality of comprehensive healthcare at primary and secondary level. However, additional evidence is needed to improve retention of information over time and to translate knowledge into clinical practice.

Antineutrophil Cytoplasmic Antibody in Lupus Nephritis: Correlation with Clinicopathological Characteristics and Disease Activity.

BACKGROUND: Lupus nephritis (LN) represents 40%-50% of all systemic lupus erythematosus (SLE) patients, and rapidly progressive glomerulonephritis is associated with significant morbidity and mortality. Antineutrophil cytoplasmic antibody (ANCA) might be involved in the pathogenesis of LN. OBJECTIVE: We evaluated the role of myeloperoxidase (MPO)-ANCA, proteinase 3 (PR3)-ANCA, and anti-glomerular basement membrane autoantibodies (anti-GBM autoAb) for the diagnosis of LN. METHODS: In this cross-sectional study, 95 SLE patients were divided into 2 subgroups: LN group (n = 60) and non-LN group (n = 35). For further analysis, we subclassified the LN group into ANCA- positive (n = 16) and ANCA-negative (n = 44) LN patients. The entire Non-LN group was ANCA- negative. The SLE disease activity index (SLEDAI) was reported for each patient. Determination of MPO-ANCA, PR3-ANCA, and anti-GBM autoAb was performed using a novel multiplex bead-based technology in all patients. Data analyses were done using SPSS, version 20. Approval was obtained from the institutional review board of Zagazig University (ZU-IRB#6000). RESULTS: Of 95 patients with SLE, 16 patients (16.84%) had ANCA-positive LN, all of which were MPO-ANCA. There was a positive correlation between MPO-ANCA and SLEDAI, as well as with class IV LN. Receiver operating characteristic analyses revealed that the sensitivity and specificity of MPO-ANCA were 81.3% and 99.8%, respectively, in discriminating LN from systemic lupus without nephritis. CONCLUSION: MPO-ANCA level was significantly correlated with SLEDAI, inflammatory markers, kidney function tests, and LN class IV.

Serum Levels of Transforming Growth Factor Beta -1 (TGF-ß1) as An Early No Invasive Marker for Diagnosis of Lupus Nephritis in Systemic Lupus Erythematosus Patients.

About 40-50% of all patients with systemic lupus erythematosus (SLE) patients are associated with significant morbidity and a poor prognosis. The transforming growth factor ß-1(TGF-ß1) is a member of cytokines families which has emerged as an important player in the pathogenesis of autoimmune diseases, including SLE. In this study we aimed to evaluate TGF-ß1 as a noninvasive diagnostic test for early diagnosis of LN and to assess the correlations between TGFß-1 and clinic-pathologic characteristics as well as disease activity of SLE. This case-control study included 188 patients with SLE, stratified into two subgroups LN group and Non-LN group. We assessed diseases activity by SLE disease activity index and measured TGEß-1 by using ELISA. Our results showed that LN patients had significant lower values of serum TGF-ß1 compared with non-LN patients (P < 0.001). Moreover, there were significant differences between LN histopathological classes. The lowest levels values of serum TGFß1 was in Class V. There were significant negative correlations between levels of TGF-ß1 and SLEDAI, fever, arthritis, proteinuria, hematuria, serum creatinine, thrombocytopenia, lymphopenia, ESR, ANA, pus cell and cellular cast's, all (P < 0.01). In lupus nephritis patients, TGF-ß1 levels were positively correlated with eGFR, C3 and C4 (P < 0.001). Linear regression analysis revealed that, eGFR, CRP, thrombocytopenia, and serum creatinine were independently correlated with TGF-ß1 among lupus nephritis patients (P < 0.001). According to Receiver Operating Characteristic analysis, the sensitivity and specificity of TGF-ß1 were 91% and 65.5%, respectively in the diagnosis of LN among SLE patients. As LN group had significantly lower values of serum TGFß1 and the values further decreased with more damage of kidney tissues and progression of SLE activity. We conclude that serum TGF- ß1 could be a valuable non-invasive marker for assessment of LN activity and organ damage.

Polyneuropathy associated with chronic hemodialysis: Clinical and electrophysiological study.

AIM: To estimate the frequency and pattern of peripheral polyneuropathy (PNP) that may affect patients maintained on hemodialysis. PATIENTS AND METHODS: The study was carried out on 60 middle-aged male patients attending the Internal Medicine Department for maintenance hemodialysis. All were subjected to a complete neurological examination. Motor and sensory nerve conduction studies of both lower limbs (the tibial, peroneal and sural nerves) and both upper limbs (median and ulnar nerves), as well as F-wave measurements of both tibial and median nerves, were done. The patients were subdivided clinically into two groups, clinically apparent neuropathy and inapparent groups. Then they were divided according to the types of peripheral neuropathy detected by electrophysiological studies into axonal, demyelinated and mixed polyneuropathy. In addition, they were divided into motor, sensory and sensorimotor groups. RESULTS: Polyneuropathy was found clinically presented in 33 (55%) cases, while evident by electrophysiological examination in 100% of the clinically apparent group (33 patients) and evident in 92.5% of the clinically inapparent group (27 patients). The frequency of pathologic electrophysiological parameters was significantly higher in patients with longer duration of hemodialysis. Axonal polyneuropathy is the most prevalent type in those patients. CONCLUSION: Peripheral polyneuropathy is a common presentation in patients maintained on hemodialysis. The longer the duration of hemodialysis, the more liability to develop PNP that can be detected earlier by electrodiagnostic studies in the subclinical cases.

Interleukin-6 and hs-CRP as Early Diagnostic Biomarkers for Obesity-Related Peripheral Polyneuropathy in Non-Diabetic Patients.

The number of obese individuals is surging in developed and developing countries. Obesity predisposes to many serious illnesses. Peripheral neuropathy (PN) is one of its major complications. Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by the adipose tissue and is believed to play a principal role in obesity complications. Meanwhile, hs-CRP is a known inflammatory biomarker. This study was designed to detect the role of serum IL-6 and hs-CRP as inflammatory biomarkers in early diagnosis of peripheral neuropathy (PN) in non-diabetic obese patients. Additionally, we aimed to explore the association between IL-6 with the clinical and electrophysiological tests of PN. This cross-sectional controlled study enrolled 150 obese patients and 50 subjects as a control group. The obese groups were subclassified according to BMI into three groups; all participants were subjected to a complete neurological examination and motor, and sensory peripheral nerve conduction studies. Serum IL-6 and hs-CRP levels were assessed using a commercially available ELISA. Our results revealed that obese patients with PN had statistically significant higher values of IL-6 and hs-CRP compared to obese patients without PN and controls (P < 0.001). Meanwhile, levels of both marker were inversely related to nerve conduction velocities (P < 0.001). Obese patients with PN had higher values of serum IL-6 and hs-CRP than diabetic patients without DPN. Because the diagnostic power of both markers in serum was significant, we conclude that they could be a useful diagnostic biomarker of PN.

Stratum corneum cytokines, structural proteins, and transepidermal water loss: effect of hand hygiene.

BACKGROUND/AIMS: There are few reports on the cytokine response to high frequency hand hygiene among health care workers (HCWs) in an occupational setting. We have observed significant skin barrier compromise consistent with chronic irritant contact dermatitis in HCWs. We hypothesized that repetitive hand hygiene would activate the epidermal inflammatory cascade and lead to changes in structural proteins and cytokines. METHODS: Keratin 6, keratin 1, 10, 11, involucrin, IL1alpha, TNFalpha, IL8, IL1RA, and IL10 were analyzed from the SC using bead-based arrays. Knuckle and dorsum samples were evaluated for HCWs (n=23) before and after repetitive hand hygiene and compared with those of age-matched non-wet workers (n=23) without hand skin irritation. Erythema, dryness, and barrier integrity were measured. RESULTS: Transepidermal water loss (TEWL) was higher for HCWs but unchanged with exposure. IL1alpha and TNFalpha were highest in control volar forearm. IL1alpha, TNFalpha, and IL8 were significantly lower in HCWs than controls despite higher erythema, dryness, and TEWL. Decreases in keratin 1, 10, 11, increases in keratin 6, and reduction in IL1alpha, TNFalpha, and IL8 were seen after hand hygiene. CONCLUSION: This preliminary study showed significantly lower SC biomarker levels in HCW compared with controls and regional differences between the hand and forearm. Exposure to repetitive hand hygiene results in substantial chronic skin irritation without time for barrier recovery between work periods. The impact on SC structural proteins and cytokines has many commonalities with chronic inflammation, although mechanistic questions remain.