Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

The Non-Significant Benefit of BCG Vaccination for the Treatment of Iranian Patients with Type 1 Diabetes up to 48 Weeks: A Controversial Result.

Background:There has been considerable interest in target immunotherapy in patients with diabetes. This study was designed to identify the effect of BCG vaccination in the treatment of Iranian patients with longstanding diabetes mellitus type 1. Methods: After approval of the cross-sectional study protocol by the ethics committee under number IRCT2017042919940N2, a total of 19 Iranian volunteers with diabetes mellitus type 1 completed this 48-month study. These patients received three 0.1 ml intradermal injections of BCG vaccination in weeks 0, 4 and 24. The serum level of glucose, HgbA1C and c-peptide was measured before and serially after the interventions. Insulin requirements were recorded for each patient in different weeks as the mean and standard deviation. Results: This study showed a decrease in the blood sugar level of 171.15±75.54 mg/dL in baseline to 133.77±76.97 mg/dL in 12 weeks after the first dose of BCG vaccination in these patients. There was no significant change in the mean± SD of serum blood sugar, HgbA1C and c-peptide after BCG vaccination in the baseline and week 48. Conclusion: Our results showed that small doses of BCG vaccination were not effective in long-term treatment of Iranian patients with diabetes mellitus type 1 up to 48 weeks.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry.

BACKGROUND: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers. METHODS: This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006. RESULTS: A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %). CONCLUSIONS: Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases.

Quantitative serum determination of CD3, CD4, CD8, CD16, and CD56 in women with primary infertility: The role of cell-mediated immunity.

Objective: Cellular adaptive immunity plays an essential role in the etiology of primary infertility. This study aimed to measure the T-lymphocyte subpopulations and natural killer (NK) cells in infertile women compared with healthy ones. Materials and Methods: From January to September 2021, we conducted this cross-sectional study among women with primary infertility, and healthy women were referred to Isfahan Fertility and Infertility Center affiliated with Najafabad University of medical sciences in Isfahan, Iran for immunological investigations. For each person, we determined quantitative serum measurements of CD3, CD4, CD8, CD4/CD8, CD16, CD56, and CD56+16. Results: This study included one hundred and fifty-one infertile women with a mean age of 31.4±4.7 years and 46 healthy women with a mean age of 31.5±3.4 years. Compared to the controls, immunophenotyping findings in infertile patients revealed a significant drop in CD8 T cells [p=0.01, 95% confidence interval (CI) 0.53 to 4.57] and the percentage of CD 56 NK cells (p=0.005, 95% CI 0.74 to 4.03) in infertile patients. Conclusion: Despite having a normal quantity of CD3 T cells, infertile women had lower CD8 T cells and CD56 NK cells than the controls. More studies are needed to confirm the role of cell-mediated assessments as a screening test in patients with primary infertility.

Immunoglobulin G4 deficiency can be a new entity for primary recurrent miscarriage: Successful pregnancy in two cases after treatment with intravenous immunoglobulin.

Recurrent miscarriage is one of the complications of pregnancy in which the potential role of immunologic factors has already been mentioned. Here, two young women with recurrent miscarriage were consulted in the infertility center. The diagnosis of immunoglobulin G4 (IgG4) deficiency was made through the reduction of IgG4 Ig levels and normal total IgG titer. Considering this abnormality, intravenous Ig 200 mg/kg was started monthly, and they both had successful pregnancies. Little is known about IgG4 deficiency in women with recurrent miscarriage. IgG4 deficiency should be taken into account in these patients. It is expected that these results will shed further light on the feasibility of intravenous Ig for women with recurrent miscarriage.

The Effect of Adaptation Training on Controlling Maladaptation Behaviors in Adolescents with Asthma Based on Roy Adaptation Model.

BACKGROUND: Asthma is a common long term inflammatory disease during adolescent. Absence of school education and reduction of mental and social mindedness are among the most common problems found in adolescents with asthma. Therefore, the present study was aimed to examine the effect of Roy adaptation model on controlling maladaptation behaviors in adolescents with asthma. MATERIALS AND METHODS: This study is a semi-experimental research that was conducted with the participation of all adolescents with asthma referred to the Asthma and Allergy Clinic of Shariati Hospital. Random sampling was used for a total of 64 adolescents to have two groups of intervention and control. Data collection was through a questionnaire based on the Roy's Adaptation Model. Over six weeks, adolescents were trained in six two-hour sessions. Data were analyzed by descriptive and analytical statistics consisting of Mann-Whitney, ANOVA, paired t-test and independent t-test. RESULTS: The mean age of adolescents with asthma in the intervention and control groups was 15.8±3.5 and 14.8±3.5 years, respectively. Also, the mean score of maladaptation behaviors in four physiological, self-concept, role-function and interdependence modes had a significant difference in intervention group before and after training (p<0.001), but there was no significant difference in all modes before and after intervention in control group (p>0.05). CONCLUSION: Given the effect of Roy adaptation model on the different aspects of maladaptation behaviors in adolescents with asthma, it is recommended to use this model as a healthcare intervention for controlling maladaptation behaviors in adolescents with other chronic disease.

Effect of Orem's Self-Care Model on Perceived Stress in Adolescents with Asthma Referring the Asthma and Allergy Clinic, Isfahan, 2014.

BACKGROUND: Incidence of asthma in adolescents leads to variations in family status, roles and interaction with peers for them, which could be a source of stress and psychological tensions in them. Therefore, the present study was conducted to investigate the effect of Orem's self-care model on perceived stress in adolescents with asthma. METHODS: In this semi-experimental study conducted from April 2013 to February 2014, 64 asthmatic adolescents referring Shariati Hospital, Isfahan were enrolled by simple random sampling and the patients were assigned to two groups of control and intervention. Then, Orem's self-care model-based training was implemented throughout eight sessions of two hours each and the Cohen Perceived Stress Scale was administered to both groups prior to and two months after the completion of the training. The data were analyzed by descriptive and analytical statistics consisting of paired t-test, independent t-test, Chi-square and Mann-Whitney using SPSS Version 20. RESULTS: Mean age of the participants was 14.15±3.12 years in the intervention group and 15.21±3.09 years in the control groups. 68.8% and 59.4% of the participants were male in the intervention and control groups, respectively. Independent t-test indicated a significant difference in the mean scores of perceived stress in the intervention (25.46±5.31) and control groups (28.90±5.27) after the training. Also, the result of paired t-test indicated a significant difference in the mean score of perceived stress between before (29.18±5.27) and after (25.46±5.31) training. CONCLUSION: As the training based on Orem's model had a positive effect on declining perceived stress in asthmatic adolescents, continuation of using these training interventions could contribute to ultimately achieving positive outcomes in health functions of these patients.

Efficacy of atorvastatin and antihistamines in comparison with antihistamines plus placebo in the treatment of chronic idiopathic urticaria: a controlled clinical trial.

Chronic idiopathic urticaria is defined as recurrent hives occurring for at least 6 weeks. In the majority of cases, there is no identifiable underlying etiology despite extensive evaluation. A subset of these patients is classified as having autoimmune urticaria defined by the presence of a functional IgG antibody to the α subunit of the high-affinity IgE receptor (FceRIa) or to IgE. The aim of this study was to evaluate the effects of the drug atorvastatin in patients with chronic urticaria compared to the placebo.In this single-blind study, 50 patients suffering from chronic urticaria (15-45 years old) were selected and divided into two groups by simple randomization method. The first group was treated with atorvastatin and antihistamines and the second group (control group) was treated with placebo and antihistamines for 3 months. Urticaria severity was measured by score index, before and after the treatment course: ASST (autologous serum skin test) was performed for all patients and sera were collected to measure cytokines. In cases, IL-5 decreased and IL-10 increased after treatment compared to the time point before treatment (p<0.05). All patients with severe utricaria according our scoring, had positive ASST.The patients with severe urticaria identified by urticaria score and ASST positivity had chronic idiopathic urticaria. By prescribing the atorvastatin plus antihistamines in severe and resistant forms of urticaria, the use of more toxic medications like cytotoxic drugs may be avoided.