Leptin gene Polymorphism and Leptin protein levels in Pediatric Autoimmune Hepatitis.

BACKGROUND: Leptin plays a role in regulating energy balance, immunity, and inflammation. Studies suggest higher leptin levels might be associated with various autoimmune diseases. Most of them were in adult. To our knowledge, our study is one of the few that describe serum leptin level and leptin gene polymorphism in children with autoimmune hepatitis (AIH). OBJECTIVE: Our study aims to explore the association between serum leptin level and genetic variations in leptin gene with the likelihood of AIH in children. PATIENTS AND METHODS: Thirty-one children with AIH and 29 healthy children serving as a control group were included. Serum leptin levels were measured by ELISA assays. Leptin rs2167270 genotyping was done using the real time-PCR. The relationship of serum leptin level and leptin gene polymorphism with patients' data was studied. Patients follow up to assess treatment response. RESULTS: Children with AIH had significantly higher levels of leptin compared to healthy controls. GG genotype was significantly more prevalent in the AIH group compared to controls. CONCLUSION: High serum leptin levels and leptin gene polymorphism may play a role in AIH development. It is worthy to recognize if leptin can serve as diagnostic and/or therapeutic target in AIH in children.

Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune illness with a growing prevalence in many populations. Few studies have examined genetic predisposition to SLE, so we aimed to examine the clinical impact of the genetic polymorphisms MECP2 rs2734647and TIRAP rs8177374 on the outcomes and therapeutic precision of SLE with and without nephritis. This study included 110 SLE patients-divided into 63 with lupus nephritis (LN), and 47 without nephritis-and 100 controls. Laboratory measurements including CRP, ESR, ACR, CBC, anti-ds-DNA, vitamin A, C3, and C4 were carried out, along with genotyping of MECP2 rs2734647and TIRAP rs8177374 by real-time PCR and sequencing. Treg %, vitamin A, C3, and C4 were lower, whereas Th17 % was higher, in patients vs. controls (p < 0.001). The T allele of MECP2 rs2734647 was higher in LN than in non-nephritis and control subjects. Moreover, the T allele of TIRAP rs8177374 was higher in LN than in non-nephritis and control subjects. The MECP2 and TIRAP genes could play a role in predisposition to SLE, and can also predict disease progress to nephritis, helping to personalize medicine.

Serum Krebs von den Lungen-6 and lung ultrasound B lines as potential diagnostic and prognostic factors for rheumatoid arthritis-associated interstitial lung disease.

INTRODUCTION: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (RA-ILD) is a serious systemic RA manifestation with high mortality that needs proper, accurate, and sensitive assessment tools. OBJECTIVES: Firstly, evaluate serum Krebs von den Lungen-6 (KL-6) levels and lung ultrasound B lines (LUS B lines) score in RA-ILD correlating them with the severity of ILD assessed by high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs). Secondly, determine cut-off values for LUS and KL-6 in RA-ILD assessment and outcome prediction. METHODS: A case-control study included seventy-five RA-ILD patients with an equal number of matched RA patients without ILD. Clinical assessment includes DAS-28 and PFTs, laboratory assessment of serum KL-6 by latex-enhanced immunoturbidimetric assay, and radiological evaluation of ILD using semiquantitative CT grade and LUS B lines. RESULTS: RA-ILD patients had significantly higher serum KL6 compared to those without ILD (1025.5 ± 419.6 vs. 237.5 ± 51.9, p ≤ 0.001). Serum KL6 was positively correlated with HRCT and LUS scores (r = 0.93, r = 0.97, respectively) with negative correlation with FVC% and FEV1% (r = - 0.93, r = - 0.91, respectively). LUS was positively correlated with KL6 and HRCT (r = 0.97, r = 0.944, respectively) while, negatively correlated with PFTs. Cut-off values of KL6 and LUS were 277.5 U/ml and < 5.5, with AUC 0.878 and 1, sensitivity 86.7% and 100%, and specificity 88% and 100%, respectively. CONCLUSIONS: The non-invasive, radiation-free LUS with a score < 5.5 combined with serum KL6 could be helpful for RA-ILD assessment correlating with HRCT and disease severity. Serum KL6 combined with LUS is important new and potential prognostic factor predicting poor outcomes in RA-ILD. Further large-scale, multi-center, and prospective studies are needed to confirm these findings. KEY POINTS: • Combination of the non-invasive, radiation-free LUS with a score < 5.5 and serum KL6 levels of 277.5 U/ml is recommended as prognostic tools for RA-ILD. • Easily obtainable tests such as serum KL-6, inflammatory markers, and LUS are sensitive for assessing RA-ILD and the risk of poor outcomes in patients with RA-ILD. • RA-ILD patients with higher KL6 levels, higher LUS scores had a poor prognosis with short survival. • LUS B lines could be used as the first imaging tool for the evaluation of RA-ILD decreasing the risk of HRCT radiation exposure in asymptomatic or mild RA-ILD patients.