Israel Medical Association Journal

Inborn errors of immunity (IEI) result from pathogenic germline variants. These disorders are clinically characterized by increased susceptibility to infections and immune dysregulation, often leading to reduced survival [1]. By linking specific monogenic defects to immune phenotypes, IEI serve as experiments of nature that provide powerful models for dissecting human immunology [2]. The International Union of Immunological Societies (IUIS) currently classifies IEI into 10 major categories with overlapping phenotypes [3]: combined T- and B-cell immunodeficiencies, combined immunodeficiencies with syndromic features, predominantly antibody deficiencies, diseases of immune dysregulation, congenital defects of phagocytes, defects in intrinsic and innate immunity, autoinflammatory diseases, complement deficiencies, bone marrow failure, and phenocopies of IEIs. The recent 2024 IUIS update was designed to serve clinicians and researchers and to inform the design of targeted sequencing panels that facilitate the genetic diagnosis of IEI. It lists 508 genes underlying 559 conditions [3]. Of note, molecular, cellular, and clinical investigations of IEI have transformed our understanding of disease pathogenesis and enabled effective targeted therapies.

Background: Gestational hypertensive (GH) disorders remain a major obstetric problem.

Objective: To evaluate the incidence of gestational hypertensive disorders among participants undergoing intrauterine insemination (IUI) after exposure to various levels of sperm from sperm donation (SD).

Methods: A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019. Participants conceived via IUI using SD from a single sperm bank and had a successful singleton birth. Group 1 conceived during 1–2 cycles of IUI from the same sperm donor; whereas Group 2 after 3+ cycles.

Results: Overall 171 patients (Group 1 = 81, Group 2 = 90) met inclusion criteria. Participants showed no differences in age, chronic medical conditions, or history of pregnancy complications. The groups differed in gravidity and parity. The factors positively associated with Group 1 included either preeclampsia or GH (11 [13.5%] vs. 1 [1.1%], P = 0.001) and GH alone (8 [9.9%] vs. 1 [1.1%], P = 0.014). Newborns from Group 1 had a statistically significant lower birth weight than those from Group 2 (3003 grams ± 564.21 vs. 3173 grams ± 502.59, P = 0.039). GH was more prevalent in Group 1 (P = 0.008) than a control group of 45,278 participants who conceived spontaneously. No significant differences were observed between Group 2 and the control group.

Conclusions: The incidence of GH and preeclampsia in participants was higher among those exposed to 1–2 cycles than those exposed to 3+ cycles of IUI.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progression. Riluzole has been established as the only, although modestly effective, disease modifying therapy, extending mean patient survival by 3to 6 months. Recent advances in understanding the pathophysiology mechanisms of ALS encourage realistic hope for new treatment approaches. To date, the cornerstones of the management of patients with ALS are focused on symptom control, maintaining quality of life and improving survival.

Background: Epidemiological data show significant associations of vitamin D deficiency and autoimmune diseases. Vitamin D may prevent autoimmunity by stimulating naturally occurring regulatory T cells.

Objectives: To elucidate whether vitamin D supplementation increases Tregs[1] frequency (%Tregs) of circulating CD4+ T cells.

Methods: We performed an uncontrolled vitamin D supplementation trial among 50 apparently healthy subjects including supplementation of 140,000 IU at baseline and after 4 weeks (visit 1). The final follow-up visit was performed 8 weeks after the baseline examination (visit 2). Blood was drawn at each study visit to determine 25-hydroxyvitamin D levels and %Tregs. Tregs were characterized as CD4+CD25++ T cells with expression of the transcription factor forkhead box P3 and low or absent expression of CD127.

Results: Forty-six study participants (65% females, mean age ± SD 31 ± 8 years) completed the trial. 25(OH)D[2] levels increased from 23.9 ± 12.9 ng/ml at baseline to 45.9 ± 14.0 ng/ml at visit 1 and 58.0 ± 15.1 ng/ml at visit 2. %Tregs at baseline were 4.8 ± 1.4. Compared to baseline levels we noticed a significant increase of %Tregs at study visit 1 (5.9 ± 1.7, P < 0.001) and 2 (5.6 ± 1.6, P < 0.001).

Conclusions: Vitamin D supplementation was associated with significantly increased %Tregs in apparently healthy individuals. This immunomodulatory effect of vitamin D might underlie the associations of vitamin D deficiency and autoimmune diseases. Hence, our finding provides a rationale for further studies to investigate vitamin D effects on autoimmunological processes.

Twenty years ago the Israeli Association of Allergy and Clinical Immunology was established, unifying these two fields into one speciality.