Pulmonary manifestations in a cohort of patients with inborn errors of immunity: an 8-year follow-up study

Background: Inborn errors of immunity (IEIs) are a group of congenital diseases caused by genetic defects in the development and function of the immune system. The involvement of the respiratory tract is one of the most common presentations in IEIs.Methods: Overall, 117 patients with diagnosed IEIs were followed-up within 8 years at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD). Demographic, clinical, and laboratory data were collected in a questionnaire. Pulmonary function test (PFT), chest X-ray (CXR), and high-resolution computed tomography (HRCT) scans were obtained where applicable.Results: Our study population consisted of 48 (41%) patients with predominantly antibody deficiencies (PADs), 39 (32%) patients with congenital defects of phagocytes, 14 (11.9%) patients with combined immunodeficiency (CID), and 16 (14%) patients with Mendelian susceptibility to mycobacterial diseases (MSMD). . Recurrent pneumonia was the most common manifestation, while productive cough appeared to be the most common symptom in almost all diseases. PFT showed an obstructive pattern in patients with PAD, a restrictive pattern in patients with CID, and a mixed pattern in patients with CGD. HRCT findings were consistent with bronchiectasis in most PAD patients, whereas consolidation and mediastinal lesions were more common in the other groups.Conclusions: Pulmonary manifestations vary among different groups of IEIs. The screening for lung complications should be performed regularly to reveal respiratory pathologies in early stages and follow-up on already existing abnormalities.

Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association

PurposeHeterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis.MethodsGenetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect.ResultsNGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement.ConclusionWe describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.

Adaptive Phage Therapy in the Treatment of Patients with Recurrent Pneumonia (Pilot Study)

Aim. To evaluate the safety and efficacy of the adaptive phage therapy technique in patients with recurrent pneumonia in neurological critical care.Material and methods. The clinical study included 83 chronically critically ill patients with severe brain damage. The bacteriophage cocktail selected against specific hospital strains was administered by inhalation to 43 patients. The control group included 40 patients who received conventional antimicrobial therapy. The changes in clinical, laboratory and instrumental parameters, levels of biomarkers, microbiological and PCR tests of bronchoalveolar lavage fluid were assessed, including those in the «phage therapy with antibiotics» (n=29) and «phage therapy without antibiotics» (n=14) subgroups.Results. The groups were comparable in terms of basic parameters (age, sex, diagnosis, organ dysfunction according to APACHE II, use of vasoactive drugs) and the level of airway colonization with antibioticresistant bacterial strains. Good tolerability and absence of clinically significant side effects were observed during inhaled administration of the bacteriophage cocktail. Computed tomography on day 21 showed a significant reduction in lung damage in patients who received bacteriophages. Patients treated with bacteriophages without antibiotics had significantly lower need for mechanical ventilation. The mortality rate on day 28 did not differ significantly and was 4.7% (2/43) in the bacteriophage-treated group vs 5% (2/40) in the control group.Conclusion. The first experience of using the adaptive phage therapy technique in chronically critically ill patients in neurological intensive care demonstrated the safety of inhalational administration of the bacteriophage cocktail. The efficacy of the technique was confirmed by the treatment results obtained in the phage therapy group, which were not inferior to those in the group with conventional antibiotic therapy, while several clinical and laboratory parameters tended to improve even in patients who received bacteriophages and did not receive antibiotics.

Fatal congenital lobar emphysema in a puerpera: a case report and literature review

Background Congenital lobal emphysema (CLE) is a developmental lung abnormality usually diagnosed in the neonatal period and is rarely observed in adults. Adults with CLE are usually asymptomatic and only a small fraction may present with coughing, recurrent pneumonia and respiratory distress. In imaging studies, the most frequently affected lobe of CLE is the left upper lobe, followed by the right middle lobe. However, multilobar involvement with severe mediastinal shift is extremely rare. Case presentation We report a case of fatal CLE in a 28-year-old puerpera with postpartum respiratory failure. Chest computed tomography (CT) revealed emphysema of the right upper, middle and lower lobes resulting in adjacent atelectasis. Hyperinflation of the right upper lobe crossed the midline, leading to a deviation of the mediastinal structure to the left hemithorax and severe compression of the left lung. Conclusions Early and timely diagnosis of CLE with routine follow-up is necessary for patients. CLE, especially with multilobar involvement or mediastinal shift, could be life-threatening and should be promptly and aggressively treated to prevent severe complications.

First patient in the Iranian Registry with novel DOCK2 gene mutation, presenting with skeletal tuberculosis, and review of literature

Background Dedicator of cytokinesis 2 (DOCK2) deficiency is an inborn error of immunity characterized by cellular and humoral immunological abnormalities leading to early-onset infections. Case presentation We reported a novel case of a 27 months old girl presenting with recurrent pneumonia and a history of skeletal tuberculosis at the age of 19-month-old. Her immunological workup revealed persistent lymphopenia and low CD4 + T cell count along with elevated levels of CD19 +, CD20 +, CD16 +, and CD56 + cells. Furthermore, she had a high level of immunoglobulin (Ig) E and a slightly reduced IgM level with a non-protective antibody titer against diphtheria. The whole-exome sequencing (WES) analysis identified a homozygous frameshift deletion mutation (c.1512delG, p.I505Sfs*28) in exon 16 of the DOCK2 gene. We also conducted electronic searches in PubMed, Web of Science, and Scopus databases and reviewed the articles reporting patients with DOCK2 deficiency. The literature search yielded 14 DOCK2-deficient patients suffering from both cellular and humoral immune defects leading to early-onset infections, particularly human herpesvirus (HHV) infection. Conclusion DOCK2 deficiency should be considered in the context of severe or unusual early-onset infections, especially HHV infections, in a patient with a probable clinical diagnosis of combined immunodeficiency. We also recommended that DOCK2-deficient patients might benefit from T-cell receptor excision circle (TREC) assay as part of the routine newborn screening program.

Autoimmune Hemolytic Anemia Due to Spondyloenchondrodysplasia with Spastic Paraparesis and Intracranial Calcification due to Mutation in ACP5

Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in ACP5, playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old. He had short stature, platyspondyly, metaphyseal changes, intracranial calcification, spastic paraparesis, and mild intellectual disability. He also had recurrent pneumonia attacks. The clinical diagnosis of SPENCD was confirmed by sequencing of the ACP5 gene, and a homozygous c.155A > C (p.K52T) variation was found, which was reported before as pathogenic. In conclusion, in early onset chronic autoimmune cytopenias an immune dysregulation may often have a role in the etiology. Associating findings and immunologic functions should be carefully evaluated in such patients in the light of the literature. The present case shows the importance of multisystemic evaluation for the detection of SPENCD that has a monogenic etiology.

B Cell Subsets in Colombian Adults With Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia

Purpose. To evaluate lymphocyte’s populations and B cell subsets in patients presenting with PAD diagnosed with bronchiectasis or recurrent pneumonia seen in Cali (Colombian Southwest region). Methods. 16 patients with PAD, 20 with bronchiectasis or recurrent pneumonia and 20 healthy controls were included. Lymphocyte populations (T, B & NK cells) and B cell subsets were evaluated in Peripheral Blood mononuclear cells (PBMC) using flow cytometry, using the T/B/NK reagent and the pre-germinal center antibody panel proposed by the EUROflow consortium, respectively. Clinical and sociodemographic data was collected (hospital records and interview). EUROclass and the classification proposed by Driessen et al were implemented. Results. B cell subsets were disturbed when compared to the age range matched healthy donors. Among B cell subsets,memory B cellcompartment was the most affected, especially switched memory B cells. Four participants were classified as B- and two CVID as smB-Trnorm and smB-21lo groups according to EUROclass classification. The most frequent pattern proposed by Driessen et al were B-cell production and germinal center defect. PAD participants also showed alteration in the B cell subsets correlation. Non-PAD participants with pulmonary complication also had alteration in B cell subsets.