Vol 1, No 1 (2018)
Although comprehension of the molecularbasis of primary immunodeficiency diseases (PID) provides unique insight into the functioning of the immune system, translational research is also needed to provide better care to affected individuals. Many institutions and academic departments have been established to provide training and encourage collaborative research on the immune system and related disorders. In Iran, one of the frontiers of PIDs in the Middle Eastern region, considerable progress in basic and clinical immunology has been achieved during the last three decades. During this period, massive improvements have revolutionized the management of PIDs in the country, from educational and research related aspects to diagnostic procedures and treatments available to Iranian PID patients. In this review, we seek to elucidate the current status of PIDs in Iran from different angles and to speculate upon the opportunities that the future may bring.
Background/objectives: Common variable immunodeficiency (CVID) is a heterogeneous syndrome described by defective antibody production and occurrence of multiple clinical manifestations including autoimmune, lymphoproliferative, and granulomatous diseases. Genes within the major histocompatibility complex (MHC) region have previously been reported to be involved in the pathogenesis of the disease.
Methods: To elucidate the human leukocyte antigen (HLA) association, PCR was performed to clarify type HLA B, DR, and DQ alleles in a large sample of Iranian and Swedish CVID patients.
Results: No HLA association was observed between Iranian patients with “sporadic” CVID (n=50) and controls. A slight HLA association (B8, DR3, DQ2) was found in Swedish CVID patients (n=95). However, the latter was entirely due to an association in the familial form of the disease. Using 13 informative multiplex families with patients affected by CVID and IgA deficiency (IgAD), shared haplotypes such as HLA-B8-DR3-DQ2; HLA-DR1-DQ5; HLA- DR4- DQ3, and HLA-DR7-DQ2 were observed.
Conclusions: Based on our results, we hypothesize that only the familial form of CVID/IgAD may have a common HLA-associated genetic background, whereas “sporadic” cases show no HLA association.
Backgrounds/Objectives: X-linked agammaglobulinemia (XLA) is a primary immunodeﬁciency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene. It is characterized by severely reduced numbers of peripheral B cells and a significant deﬁciency in all serum immunoglobulins. In the present study, the impact of mutation severity on the clinical and immunological characteristics of XLA patients was evaluated.
Methods: Mutation analysis was performed in 19 XLA patients by PCR assay to identify variations in theBTK gene. Subsequently, the western blotting technique was applied for measuring BTKexpression and function. A genotype-phenotype correlation was investigated regarding the impact of mutation severity on clinical and immunological parameters.
Results: Mutation detection in theBTK gene revealed missense mutations in 9 patients, nonsense mutations in 3 cases, splicing site defects in 5 patients, and small in-frame deletions in 2 patients; 31% of patients displayed normal BTK expression. A significant correlation was found between types of BTK mutation and BTK expression.
Discussion: Generally, genotype-phenotype correlation studies on XLA disease seem to be very controversial. The results of the correlation analysis in the present study could indicate that evolution of the disorder is not completely similar in all cases, even with the same mutation.
Chediak-Higashi syndrome (CHS) is an inherited primary immunodeficiency with an autosomal recessive pattern which is usually identified by partial albinism and frequent pyogenic infections. Herein, we report the interesting case of childhood onset with the main presentation of chronic diarrhea which was treated with dexamethasone and various antibiotics for achronic fever. The patient was givenetoposide once a week and intravenous immunoglobulin monthly thereafter, which caused partial shrinkage in the size of the liver and spleen and improved the patient’s clinical condition. Since CHS is invariably lethal after entering the accelerated phase and early diagnosis may facilitate bone marrow transplantation as the only curative treatment, careful examination in unusual patients without multiple recurrent infections or diagnosed hemophagocytic lymphohistiocytosis should be considered.