Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features.

Background: Combined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions. Methods: We analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations. Results: A total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, were clinically diagnosed with antibody deficiencies before genetic evaluation. Patients with ATM and WAS mutations had the latest age of onset and the lowest age of diagnosis, respectively. Autoimmune disorders were diagnosed in 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. Lymphoproliferation, particularly hepatosplenomegaly, was significantly higher in patients with autoimmunity (p=0.004). Syndromic CID patients with autoimmunity had significantly lower IgG levels. Hematologic autoimmunity mainly immune thrombocytopenic purpura was the most frequent autoimmunity among major groups of ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations, however ATM-mutated patients present more diversified involved organs including rheumatologic, gastrointestinal and dermatologic autoimmunity. Conclusion: About 18% of patients with monogenic syndromic CIDs developed autoimmunity, mainly in the form of hematological immune diseases. Autoimmunity could be an early-onset involvement with a potential diagnostic impact on suspicious cases of syndromic CIDs.

Rectal measurements and their correlation with bowel habits: Evaluation by trans-abdominal ultrasound in children with functional constipation.

AIM: Constipation is one of the most common complaints in childhood affecting the quality of life of both children and parents. This study intends to investigate rectal measurements on ultrasound and their relationship with bowel habits. METHODS: In this cross-sectional study, 100 children with functional constipation (FC) referred to a single hospital between 2018 and 2019 were enrolled. After obtaining informed consent, a questionnaire including demographic and constipation characteristics was completed, and a physical examination including digital rectal examination (DRE) was performed. Complete abdominopelvic ultrasound was then performed. Target measurements included rectal transverse diameter (RTD), rectal anterior wall thickness (RAWT) and the presence of faecal impaction. RESULTS: One hundred children with a mean age of 7.68 ± 3.30 years were present in the study. The mean duration of constipation was 15.86 ± 13.34 months. In 14% of children, painful defaecation was reported. 88% of children had some degree of faecal incontinence. According to the ultrasound findings, the mean RTD and RAWT were 3.39 ± 0.73 cm and 2.77 ± 0.68 mm, respectively, and faecal impaction was present in 70% of cases. There was a positive correlation between RTD and RAWT with age, duration of constipation and the presence of hard stools, and there was a negative correlation with frequency of defecation (P < 0.05). CONCLUSION: RTD and RAWT increased with increasing constipation duration and the presence of hard stools and decreased with increasing frequency of defaecation. DRE could be omitted from the initial clinical assessment if you had access to reliable ultrasound data.

Diagnostic Approach to the Patients with Suspected Primary Immunodeficiency.

BACKGROUND AND OBJECTIVE: Primary immunodeficiency diseases (PIDs) are a group of more than 350 disorders affecting distinct components of the innate and adaptive immune systems. In this review, the classic and advanced stepwise approach towards the diagnosis of PIDs are simplified and explained in detail. RESULTS: Susceptibility to recurrent infections is the main hallmark of almost all PIDs. However, noninfectious complications attributable to immune dysregulation presenting with lymphoproliferative and/or autoimmune disorders are not uncommon. Moreover, PIDs could be associated with misleading presentations including allergic manifestations, enteropathies, and malignancies. CONCLUSION: Timely diagnosis is the most essential element in improving outcome and reducing the morbidity and mortality in PIDs. This wouldn't be possible unless the physicians keep the diagnosis of PID in mind and be sufficiently aware of the approach to these patients.