Immunology and Genetics Journal
Volume:2 Issue: 4, Dec 2019

“Precision medicine” is the use of therapy that targets the molecular basis of a patient’s disease process. This approach is increasingly well-established in treatment of monogenic disorders of immunity, including primary immunodeficiencies and primary immune regulatory disorders. This is due to the exquisite detail with which many immune pathways have been defined, and the wide variety of immune modulatory medications that target these pathways. Here we review many of the most effective uses of this approach and suggest a framework for classifying these strategies.

Primary immunodeficiencies contain a set of several different diseases. Giving the fact that their clinical outcome ranges from mild to potentially life-threatening, detecting the patients with these diseases in the neonatal period is considered as the main goal of efforts that are currently being made. It has been reported that T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are circular DNA segments produced in T and B cells during their maturation in the thymus and bone marrow, respectively. Fortunately, excision circles can be reliably quantified using real-time quantitative PCR techniques.

  Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifest a wide clinical variability such as gastrointestinal (GI) disorder.

A total of 240 patients with CVID were enrolled in this study. The patients were evaluated for demographic data, clinical manifestations, and immunologic profile.

In demographic data, the frequency of consanguinity and mortality rate were higher in patients with GI manifestation than those without GI manifestation. History of GI manifestations was evident in 147 patients (61.3%). The most common GI manifestation in patients with CVID was chronic diarrhea (29.6%). The prevalence of GI disease was 59 of 102 (57.8%) in female patients and 88 of 138 (63.8%) in male patients. The frequency of recurrent infection was higher in patients with GI manifestation than in those without GI manifestation. Also, CVID patients with GI manifestations had lower WBC and CD4+ T cells than patients without GI manifestations.

CVID patients are at increased risk of infectious conditions in the GI tract; hence GI manifestations are one of the most important presentations in CVID patients which can appear as a first manifestation or appear during the course of disease.

hyper-IgM (HIGM) syndrome is characterized by normal to increased serum IgM and very low or undetectable IgG, IgA, and IgE. HIGM (also known as class-switch recombination (CSR) defects) patients manifest different clinical manifestations such as autoimmune disorders. Aim of present study was to evaluate demographic data, clinical manifestation and immunological findings in HIGM patients.

Clinical features and immunological data were collected from the 79 Iranian HIGM patients’ medical records diagnosed in Children’s Medical Center in Iran. To compare clinical records and laboratory data, all HIGM patients were classified into two different groups patients with autoimmune disease and patients without autoimmune diseases.

A total of 79 patients (60 male and 19 female ) with median (IQR) age at the time of the study of 12 (6-22.45). Autoimmunity diseases were seen in 19 patients (23.75% , 3 females and 16 males). Among the noninfectious manifestations, the hepatomegaly and spelenomegaly were significantly higher in patients with autoimmunity (p= 0.006) than patients without autoimmunity (p=0.006). The most common autoimmune presentations among HIGM patients were ITP (32%), juvenile rheumatoid arthritis (16%), autoimmune hemolytic anemia (11%) and Sclerosing cholangitis (11%), Gullain-Barré syndrome, Evans syndrome, diabetes mellitus and chrohn's disease.

The relation between HIGM syndrome and autoimmunity disorders could lead to sever clinical complications. So, we suggested that immunologists to be aware of this complications.

NF-κB pathway is a complex protein playing an important role in regulating lymphocyte development, immune responses, inflammation, cell proliferation, and cell death. The NF-kB signaling pathway has been described to be associated with canonical and noncanonical pathway. The canonical pathway utilizes NF-kB1, whereas the latter pathway involves NF-kB2, which is the cornerstone of the non-canonical NF-kB pathway, and has been shown to be critical for the development of secondary lymphoid organs, B cell development, and the humoral response to T-dependent and T-independent antigens. In this study, we investigated the patient with chief complain of low body temperature as well as feeling cold even in the warm seasons since 15 years ago. We reported a middle age man with mild lymphopenia and no significant infection, but hypothermia with significant chills even in the warm seasons with a mutation in NF-κB2 pathway.

NEMO (NF-κB essential modulator) is a regulatory factor involved in signaling pathways of innate and adaptive immune system. Hypomorphic mutation of IKBKG gene on X chromosome leads to X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency. The affected boys presented developmental phenotype with hypotrichosis, hypohidrosis; hypodontia with conical incisors; and susceptibility to pyogenic bacteria, mycobacteria, and viruses. Most of them have impaired antibody response to polysaccharide antigens. Here, we presented the case report of 7 years old Iranian boy with NEMO-deficiency and unusual Aspergillus infection.