Immunology and Genetics Journal
Volume:4 Issue: 1, Mar 2021

The newest member of the coronavirus family, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has caused a pandemic (after being endemic in Wuhan, China) and is threatening to the health of every person on the planet. Nearly 1.5 years after the coronavirus disease 2019 (COVID-19) worldwide challenges, a gold-standard, highly effective anti-viral therapy is still undiscovered. The urgency of this pandemic has forced all scientists to tackle this problem using any logical mode of therapy. One such approach is modulating and manipulating the host’s immune response using immunotherapy against SARS-CoV-2 infection and its collateral complications. This review article aims to present an update on the immunopathogenesis of SARS CoV-2, and how it, directly and indirectly, deteriorates the patients’ condition. The latest findings of preclinical and clinical trials using passive immunotherapy in the context of the COVID-19 are compiled as well.

Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is an inborn error of immunity characterized by a heterogeneous spectrum of manifestations, including enteropathy, immune dysregulation, and autoimmune disorder. Joint involvement has been less frequently reported, and limited data regarding its clinical presentation in LRBA deficiency has been published.

We reported an Iranian girl who was initially presented with recurrent respiratory tract infections and otitis media, later complicated by arthritis, growth failure, and organomegaly. The diagnosis of LRBA deficiency was confirmed by the identification of a novel homozygous missense variant in the LRBA gene (c.7742T>A, p.M2581K). Along with this report, a literature review focused on joint involvement, on 26 patients with LRBA deficiency was performed.

Non-infectious manifestations such as joint involvement have a broad spectrum in LRBA deficiency. For the timely diagnosis and appropriate clinical management, LRBA deficiency should always be kept in mind as a differential diagnosis in patients with joint involvement and clinically typical immune dysregulation.

Selective IgA deficiency (SIgAD), is known as the most common antibody deficiency. This study, investigated the respiratory disorders among these patients.

In this retrospective descriptive study, the data of patients with SIgAD in “Iranian Primary Immunodeficiency Registry” were extracted. Then, demographic characteristics, frequency and type of respiratory disorders, in addition to immunologic findings were gathered and analyzed by SPSS software.

One hundred and twenty three patients with SIgAD (78 males/45 females), with the mean age of 18± 9.6 years old were investigated. Respiratory complications (recurrent cold, chronic cough and pneumonia), were the first presentation in 45% of the patients, and respiratory system involvement was detected among 66 patients (54.1%). The prevalence of pneumonia, otitis media and sinusitis, were 33.3%, 12.5% and 20.7%; respectively; which were significantly reduced after the diagnosis (P<0.05). Bronchiectasis had also been found in five patients (4.1%).

Respiratory problems were shown to be common presenting disorders in SIgAD. Early diagnosis and appropriate therapy could be crucial for better protection, and avoidance of severe respiratory complications in these patients.

Elevated serum levels of IgM and recurrent infections, mainly respiratory tract infections, could be the presenting features in some ataxia-telangiectasia (AT) patients, and may initially be misdiagnosed as hyper-IgM (HIgM) syndrome. Class switch recombination (CSR), which is defective in HIgM syndrome, is an important mechanism in the maturation of B lymphocytes to produce different isotypes of antibodies in response to antigen stimulation.

The clinical manifestations and laboratory findings of 16 cases with low IgA and IgG levels, and normal to elevated IgM levels with CSR defect are reported.

In 16 cases, the median age at onset of the diseases, and median age at the time of the diagnosis were 1 year (interquartile range [IQR] = 1.6), and 4 years (IQR = 3.1), respectively. Two of the patients (12.5 %) died due to respiratory infection. In this study, Out of the studied population, four were male (25%), and 12 were female (75%). Most of the patients had consanguineous parents (81.3 %). All of the patients had ataxia, and 15 patients had telangiectasia (93.8 %), and one of the cases had malignancy (dermatofibroma). Also, 15 patients presented infections (93.8 %). Autoimmunity was seen in three patients (18.8 %). In addition, some of the patients manifested hepatosplenomegaly (31.3 %) and thrombocytopenia (18.8 %). Neurological manifestations, such as visual impairment (12.5 %), epilepsy (6.3 %), and tremor (12.5 %), were also present.

AT patients with HIgM phenotype and CSR defect, compared to other AT patients, may present different clinical manifestations, such as various infections. Considering their manifestations, the management and treatment of these patients are necessary.

APECED is a rare autosomal recessive disease, caused by mutations in the AIRE-gene resulting in a failure of T-cell tolerance, clinically characterized by multiple autoimmunopathies. The objective of the study was to determine the clinical and genetic features and consequences of APECED in a single-centre Ukrainian cohort of patients.

Out of five families, eight patients with APECED were included in the study. Family history and clinical information of each patient was collected; laboratory studies aimed at identifying endocrine disorders, other autoimmunity, and infections was done. Genetic testing by NGS was performed in four out of five families. Patients were included in the study after the written informed consent had been signed by their parents/legal guardians.

In most patients, the onset of the disease was noted in childhood with manifestations of hypoparathyroidism and/or candidiasis. Adrenal insufficiency was associated later. Diabetes mellitus, hypothyroidism and hypogonadism were observed as other endocrinopathies. Five of eight patients (62.5%) developed autoimmune hepatitis, two patients suffered from autoimmune lung lesions, and two developed enteropathy. Two patients were diagnosed with brain damage: psychosis and autoimmune encephalitis. All the patients that we examined were homozygous carriers of the Finn major mutation R257X (c.769C> T) of the AIRE gene.

One or two endocrinopathies in combination with recurrent candidiasis are the key to a diagnosis of APECED. Most patients also develop organ autoimmunopathy. The mutation R257X (c.769C> T) of the AIRE-gene is predominant in the population of western Ukraine.

Common variable immunodeficiency (CVID), is generally recognized as the most frequent type of Symptomatic primary immunodeficiencies (PID). Mutations in lipopolysaccharide-responsive beige-like anchor protein (LRBA) gene, are the most common genetic alterations amongst CVID patients. To date, there are no published studies to compare clinical and immunologic features of LRBA-deficient patients with those who do not harbor any known genetic mutations. Therefore, this study aims to compare the clinical manifestations and laboratory findings of Iranian patients with LRBA-deficiency and CVID with no known genetic alterations.

We performed a longitudinal study on patients who had been diagnosed with CVID. Demographic and clinical features were obtained via the databank of the Iranian Registry of Primary Immunodeficiencies, and the direct interviews with patients. To assess the presence of LRBA or other genetic mutations, whole-exome sequencing (WES) was used. Immunologic characteristics of patients were evaluated using flow cytometry, nephelometry, and conventional blood counts. The current study is conducted at Tehran’s Children Medical Center and is approved by the ethics committee of Tehran University of Medical Sciences.

Between March 2013 and October 2019, we enrolled 30 patients with LRBA-deficiency and 13 patients with CVID, who had no identified genetic mutations. Regarding clinical features, there were no significant differences for the prevalence of infections at different sites (lung, sinuses, and middle ear) among the two groups (all P > 0.05). However, the incidences of autoimmune disorders and enteropathy were significantly higher among LRBA-deficient cases (P < 0.001). In serum levels of immunoglobulins, there were significant differences for IgG and IgM between the two groups (P of 0.014 and 0.004, respectively); however, this was not seen for IgA and IgE levels. Likewise, we did not see any significant differences for the cluster of differentiation (CD) markers between the two groups (all P > 0.05).

Compared to the CVID patients with no identified genetic mutations, LRBA-deficient patients have a significantly greater chance of parental consanguinity and developing autoimmune disorders and enteropathy, and have significantly higher values of serum IgG and IgM. The rate of infectious complications and other basic laboratory features, do not show significant differences between the two groups.

Congenital agammaglobulinemia is an inborn error of immunity, resulting in the impairment of effective antibody production. Agammaglobulinemia may be due to X-linked or autosomal genetic abnormalities. The primary defect in X-Linked agammaglobulinemia (XLA) and autosomal recessive agammaglobulinemia (ARAG) is the B cell precursors’ failure to mature B-lymphocytes and, ultimately, plasma cells. This study aims to evaluate the differences in clinical and paraclinical characteristics of XLA and ARAG patients.

A total of 58 patients were enrolled in this retrospective study. The data were extracted from the Iranian primary immunodeficiency registry (IPIDR). Forty-eight of the patients were diagnosed with XLA, while the other ten were diagnosed with ARAG. Measures including demographic data, clinical manifestations, and laboratory data of the patients were compared between the groups.

Patients with ARAG, presented manifestations at an earlier age and had a lower diagnosis delay compared to XLA patients. However, the mortality rate was not significantly affected. The pattern of organ involvement also differed between the two groups, as patients with ARAG showed manifestations that are more chronic in nature (e.g., autoimmunity, lymphoproliferation, and allergy). In contrast, XLA patients were more prone to infections and other associated complications (e.g., meningitis, sinusitis, diarrhea, and bronchiectasis). Meningitis was exclusively observed in the XLA group. The number of CD19+ B cells was significantly higher in the ARAG group (P=0.002), While the level of IgM was significantly higher in the XLA group (P=0.045).

Identifying the clinical presentations of XLA and ARAG, may assist clinicians in early diagnosis in the setting of limited available genetic studies.

Leukocyte Adhesion Deficiency (LAD) is a rare, inherited, immunodeficiency disease which is caused by defects in the leukocyte adhesion process. The migration of leukocytes to the blood vessel’s wall, needs multiple steps called adhesion cascade. In LAD, defects in rolling, integrin activation and firm adhesion of the leukocytes have been described.

In this study, we selected 67 patients with the confirmed diagnosis of LADs, from Iranian immunodeficiency registry center. A demographic information of the clinical complications and laboratory data were obtained from all the patients to evaluate the clinical manifestations.

A total of 67 patients (38 male and 29 female), with a median age of 18 months old, were included in the present study. The first presentations were omphalitis in 28.35% of the cases, followed by delayed umbilical cord separation in 22.38% of the patients. The frequency of delayed umbilical cord separation was 41.8%, and was higher among other manifestations of our patients. Cellulitis and Omphalitis were observed in 40.3% and 38.8% of the patients, respectively. Regarding the laboratory findings, we found leukocytosis in 86.6 %( neutrophil dominant in 76.1%), and anemia in 77.6%, and thrombocytosis in 25.4% of the patients.

We indicated in the present study that the most common clinical manifestations, were delayed umbilical cord separation and recurrent infection in Iranian patients with LAD disorders. In laboratory findings, we found leukocytosis in most of the patients. CD18 was decreased in more than 90 % of the patients.