Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population.

PURPOSE: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy. METHODS: We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency. RESULTS: Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range 7 days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were also documented in about one-third of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died. CONCLUSION: MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of CID at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We are better determined to study the c.162delG RFXANK heterozygous mutation frequency in the Iranian population.

The significance of stem cell-like memory T cells in viral and bacterial vaccines: A mini review.

Vaccination has become a widely used method to induce immune protection against microbial pathogens, including viral and bacterial microorganisms. Both humoral and cellular immunity serve a critical role in neutralizing and eliminating these pathogens. An effective vaccine should be able to induce a long-lasting immune memory response. Recent investigations on different subsets of T cells have identified a new subset of T cells using multi-parameter flow cytometry, which possess stem cell-like properties and the ability to mount a rapid immune response upon re-exposure to antigens known as stem cell-like memory T cells (TSCM). One of the major challenges with current vaccines is their limited ability to maintain long-term memory in the adaptive immune system. Recent evidence suggests that a specific subgroup of memory T cells has the unique ability to retain their longevity for up to 25 years, as observed in the case of the yellow fever vaccine. Therefore, in this study, we tried to explore and discuss the potential role of this new T cell memory subset in the development of viral and bacterial vaccines.

Antibody Response Before and After the Booster Dose of Inactivated Corona Vaccine in Antibody Deficient Patients.

Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients.  Thirty patients (>12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated.  Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster. Our results indicated the need of receiving booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID.

The effect of alpha lipoic acid on passive avoidance and social interaction memory, pain perception, and locomotor activity in REM sleep-deprived rats.

BACKGROUND: Evidence shows the vital role of sleep in the modulation of cognitive functions. Sleep deprivation (SD) can disrupt learning and memory processes. SD also affects pain perception and locomotor activity. Furthermore, alpha lipoic acid (ALA) may induce antioxidant and neuroprotective effects. ALA affects memory processes, pain subthreshold, and locomotor activity. The goal of the present study was to investigate the effect of REM (rapid-eye movement) SD and ALA on social and passive avoidance memory, locomotor activity, and pain perception. METHODS: Multiple-platform apparatus was used to induce REM SD for 24 h. Three-chamber paradigm test, the shuttle box, locomotion apparatus, and hot plate were used to assess social interaction memory, passive avoidance memory, locomotor activity, and pain perception, respectively. ALA was injected intraperitoneally at the doses of 35 and 70 mg/kg. RESULTS: 24 h REM SD impaired both types of memory. In addition, ALA (35 mg/kg) reversed REM SD-induced memory impairments. However, ALA (70 mg/kg) impaired social memory with no effect on REM SD-induced memory impairments. ALA (70 mg/kg) also decreased pain subthreshold in REM SD rats. CONCLUSION: REM SD impairs social interaction and passive avoidance memory. Furthermore, ALA may exhibit a dose-dependent manner in some cognitive tasks. ALA can induce a therapeutic effect at one dose, and an impairment effect at another dose (lower or higher), while the cognitive task and the conditions are equal.

Prognosis of Guillain-Barré Syndrome in Children.

OBJECTIVE: Guillain-Barre Syndrome (GBS) is an acute polyradiculoneuropathy characterized by progressive motor weakness of limbs and areflexia. In this study, our aim was to evaluate the clinical pattern and prognosis of children with Guillain-Barre syndrome. MATERIALS & METHODS: This cross-sectional study was conducted in the Pediatric Neurology Unit of Amirkola Children's Hospital, Babol, Iran during the period of 5 years from October 2008 to September 2013. We assessed the clinical features, results of electrodiagnostic tests, functional status, treatment and outcome of 17 children diagnosed with GBS. RESULTS: Of 17 (male to female ratio = 1.6:1) children studied, all had motor weakness, 4 children (23.5 %) and cranial nerve palsies. Respiratory paralysis was found in one child requiring assisted ventilation. Antecedent illness preceding GBS was recorded in 7 (41.2%) children. The GBS subtype distribution as per electrodiagnostic studies was as follows: acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 12 (70.6%) acute motor axonal neuropathy (AMAN) in 3 (17.6%), acute motor sensory axonal neuropathy (AMSAN) in 2 (11.8%). IVIG constituted the treatment given in all of the patients. Complete recovery was observed in 16 children and the remaining one child was dependent to wheelchair. CONCLUSION: GBS in children is not poor prognostic disorder and our recommendation is administration of IVIG as soon as possible after clinical diagnosis. Except for one child who remained wheelchair bound, there was no mortality or morbidity in long-term observation. Besides, strong limitation of our study was the low number of subjects.