Selective IgA Deficiency and Allergy: A Fresh Look to an Old Story

Selective IgA deficiency (SIgAD) is the most common human primary immune deficiency (PID). It is classified as a humoral PID characterized by isolated deficiency of IgA (less than 7 mg/dL but normal serum IgG and IgM) in subjects greater than 4 years of age. Intrinsic defects in the maturation of B cells and a perturbation of Th cells and/or cytokine signals have been hypothesized to contribute to SIgAD pathogenesis. The genetic basis of IgA deficiency remains to be clarified. Patients with SIgAD can be either asymptomatic or symptomatic with clinical manifestations including allergy, autoimmunity and recurrent infections mainly of the respiratory and gastrointestinal tract. Studies analyzing allergy on SIgAD patients showed prevalence up to 84%, supporting in most cases the relationship between sIgAD and allergic disease. However, the prevalence of allergic disorders may be influenced by various factors. Thus, the question of whether allergy is more common in SIgAD patients compared to healthy subjects remains to be defined. Different hypotheses support an increased susceptibility to allergy in subjects with SIgAD. Recurrent infections due to loss of secretory IgA might have a role in the pathogenesis of allergy, and vice versa. Perturbation of microbiota also plays a role. The aim of this review is to examine the association between SIgAD and atopic disease and to update readers on advances over time at this important interface between allergy and SIgAD.

Recurrent Skin Ulcers with Facial Dysmorphism and Sinopulmonary Infections: Thinking Beyond Hyper-IgE Syndrome

Prolidase deficiency (PD) is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. It occurs due to the mutations in the prolidase gene (PEPD) that result in loss of prolidase activity. We reported here a child who had presented with features compatible with hyper-immunoglobulin E syndrome (HIES) like recurrent skin ulcers, recurrent infections, facial dysmorphism, retained primary teeth, and elevated levels of immunoglobulin E levels but with normal flow cytometric assays, which was later diagnosed as PD.

SLGT2 Inhibitor Rescues Myelopoiesis in G6PC3 Deficiency

The energy metabolism of myeloid cells depends primarily on glycolysis. 1,5-anhydroglucitol (1,5AG), a natural monosaccharide is erroneously phosphorylated by glucose-phosphorylating enzymes to produce 1,5-anhydroglucitol-6-phosphate (1,5AG6P), a powerful inhibitor of hexokinases. The endoplasmic reticulum transporter (SLC37A4/G6PT) and the phosphatase G6PC3 co-operate to dephosphorylate 1,5AG6P. Failure to eliminate 1,5AG6P is the mechanism of neutrophil dysfunction and death in G6PC3-deficient mice. SLGT2-inhibitor reduces 1,5AG level in the blood and restores the neutrophil count in G6PC3-deficient mice. In the investigator-initiated study, a 30 year-old G6PC3-deficient woman with recurrent infections, distressing gastrointestinal symptoms and multi-lineage cytopenia was treated with an SLGT2-inhibitor. A significant increase in all the hematopoietic cell lineages and substantial improvement in the quality of life was observed.

Anti-Interferon Autoantibodies in Adult-Onset Immunodeficiency Syndrome and Severe COVID-19 Infection

Adult-onset immunodeficiency syndrome due to anti-interferon (IFN)-γ autoantibodies has attracted much attention in recent years. It usually occurs in previously healthy people and usually presents as chronic, recurrent, and hard-to-control infections that can be effectively treated with aggressive antibiotic therapy. Adult-onset immunodeficiency syndrome is also referred to as AIDS-like syndrome. Anti-type I IFN (IFN-I) autoantibodies have been reported to play a significant role in the pathogenesis of coronavirus disease 2019 (COVID-19) and preexisting anti-IFN-I autoantibodies are associated with an increased risk of severe COVID-19. This review summarizes the effects of anti-IFN autoantibodies on the susceptibility and severity of various infectious diseases, including SARS-CoV-2 infection. In addition, we discuss the role of anti-IFN autoantibodies in the pathogenesis of autoimmune diseases that are characterized by recurrent infections.

Granulomatous lymphocytic interstitial lung disease as a complication of common variable immunodeficiency

Common variable immunodeficiency (CVID) is a rare immunodeficiency, the classic manifestation being recurrent infections. Other lesions are often found in CVID patients, such as malignant neoplasms, autoimmune conditions caused by abnormal cellular immunity, in addition to infectious complications. Usually, the pathological process involves the lungs. This article presents a clinical case of a patient with CVID complicated by granulomatous lymphocytic interstitial lung disease.

Genetic variants identified in children with recurrent infections

Currently, the most effective way to diagnose hereditary defects of the immune system is molecular genetic research, the results of which are evaluated in conjunction with the data of clinical and laboratory studies.Aims of the sudy: to evaluate the frequency and spectrum of rare genetic variants associated with the development of primary immunodeficiency (PID) in children with recurrent infections.Materials and methods: DNA samples from 113 children with recurrent infections were analyzed by targeted multigene sequencing of 338 PID-associated genes. Results: Pathogenic variants appropriate to the potential diagnosis of PID were identified in 8% of patients. Interestingly, 47.8% of children had variants associated with auto-inflammatory disorders.

Prospects for the use of bacterial lysates in the complex therapy of chronic adenoiditis

Introduction. Adenotomy is a common surgical procedure in childhood. In children with recurrent infections of the respiratory tract, hypertrophy of the pharyngeal tonsil, a sign of lymphoproliferative syndrome of a secondary immunodeficiency state, is characterized by reduced adaptive abilities of mucosal immunity with impaired biocenosis in chronic inflammation. Pharyngeal tonsil surgery is considered stressful in frequently ill children and therefore requires preoperative preparation. In this context, it is relevant to study the nature of changes in the factors of mucosal immunity in terms of cell destruction in the nasal secretion in the complex treatment of children with hypertrophy of the pharyngeal tonsil and chronic adenoiditis, as prevention of complications in the postoperative period of adenotomy.Aim. To increase the effectiveness of the treatment of chronic adenoiditis in children with recurrent infections of the respiratory tract using the combined effect of low-frequency ultrasonic cavitation with monochromatic unpolarized light and bacterial lysates.Materials and methods. In order to test the hypothesis about the possibility of canceling adenotomy in 77 children aged 3-6 years with hypertrophy of the pharyngeal tonsil, accompanied by chronic inflammation. The effectiveness of the complex treatment was assessed by the functional and metabolic status of nonspecific resistance factors in the nasal lavage.Results and discussion. The combined effect of low-frequency ultrasonic cavitation with photochromotherapy and bacterial lysates leads to the normalization of pathophysiological changes on the surface of the mucous membrane, leading to a balance of the qualitative and quantitative composition of the functional-metabolic status of NG, which makes it possible to postpone adenotomy. The best clinical result is observed when bacterial lysates are used in complex therapy in combination with physiotherapy in children with chronic adenoiditis and, to a certain extent, substantiate the advisability of a combined effect as a non-invasive and effective method.Conclusions. Topical bacteriolysate in a complex treatment regimen for children with recurrent infections of the respiratory tract against a background of chronic inflammation eliminates bacterial antigens and enhances the intrinsic defenses of the mucous membrane of the pharyngeal tonsil.

Immunological evaluation of patients with orthopedic infections: taking the Cierny–Mader classification to the next level

Introduction: Cierny–Mader osteomyelitis classification is used to label A, B, or C hosts based on comorbidities. This study's purpose was to define the “true” host status of patients with orthopedic infection using serologic markers to quantify the competence of their immune system while actively infected. Methods: Retrospective chart review identified patients at a single-surgeon practice who were diagnosed with orthopedic infection between September 2013 and March 2020 and had immunological laboratory results. All patients were A or B hosts who underwent surgery to eradicate infection. Medical history, physical examination, and Cierny–Mader classification were recorded. Laboratory results included complement total, C3, C4, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin E (IgE), rheumatoid factor, and antineutrophil cytoplasmic antibodies (ANCA) panel. Clinically significant results were defined as flagged abnormal. Normal complement levels and normal IgG levels were considered abnormal when infection was present. Results: Of 105 patients, 99 (94 %) had documented lab abnormalities. Clinically significant abnormalities were found in 33 of 34 (97 %) type-A hosts and 66 of 71 (93 %) type-B hosts. Eleven of 105 (10.5 %) patients were formally diagnosed with primary immunodeficiency by a hematologist. IgG deficiency, of either low or normal value, in the face of infection comprised 91 % (30 of 34) type-A hosts and 86 % (56 of 71) type-B hosts. Six (5.7 %) patients received IgG replacement therapy. Twenty-eight patients had abnormal total complement levels (low or normal): 7.4 % (2 of 34) A hosts and 40 % (26 of 71) B hosts (p=0.002). B hosts had statistically significantly lower complement levels and significantly more no-growth cultures (p<0.03). Thirteen of 14 patients with recurrent infections had low or normal IgG levels. IgM was significantly lower between reinfected patients and those without reinfection (p=0.0005). Conclusions: Adding immunologic evaluation to the Cierny–Mader classification more accurately determines patients' true host status and better quantifies risk and outcome with respect to orthopedic infection. Immunologically deficient A hosts should be quantified as B hosts. IgG deficiencies may be addressed when deemed appropriate by the consulting hematologist/immunologist. Patients with recurrent infections had significantly lower IgM levels than their nonrecurrent infection counterparts.

Patient with ataxia telangiectasia undergoing elective staging laparoscopy: a case report and literature review

Ataxia telangiectasia is a rare autosomal recessive condition which develops due to a mutation in the ataxia telangiectasia mutated gene (ATM gene). As a result of this mutation, the ability of the DNA to undergo repair is undermined. The resulting cellular demise is responsible for the diverse presentation of the clinical condition. Neurological symptoms such as cerebellar ataxia, abnormal eye movements and malignancies occur commonly. Immunodeficiency predisposes these patients to recurrent infections. Perioperative management of patients with this rare condition can be associated with increased morbidity. Therefore, it is recommended that patients with ataxia telangiectasia should be managed in a multidisciplinary center, under the supervision of senior clinicians who have the insight into the clinical needs of such patients. We report herein, the perioperative management of a patient with Ataxia telangiectasia undergoing laparoscopic procedure. Continuous....