Manish Butte

J Pak Med Assoc. 2023 Jun;73(6):1355-1357. doi: 10.47391/JPMA.7042.

ABSTRACT

Chronic granulomatous disease (CGD) is a rare, primary immunodeficiency disorder that occurs due to a defective NADPH (Nicotinamide Adenine Dinucleotide Phosphate) oxidase system. Due to the varying clinical presentation and symptom overlap with other conditions, CGD can often pose as a challenge for paediatricians. This case report describes the approach to diagnosis and management of an infant affected by CGD, with liver abscess.

PMID:37427655 | DOI:10.47391/JPMA.7042

Malays J Med Sci. 2023 Jun;30(3):112-121. doi: 10.21315/mjms2023.30.3.10. Epub 2023 Jun 27.

ABSTRACT

BACKGROUND: Intravenous immunoglobulin (IVIG) replacement therapy is increasingly in demand. This study focused on the characteristics of IVIG usage and associated factors toward the frequency status of IVIG among patients in Hospital Kuala Lumpur.

METHODS: A retrospective cross-sectional study was performed on patients who received IVIG in Hospital Kuala Lumpur. Data were extracted from the request forms for IVIG recorded in the Pharmacy Department from January 2018 until December 2019. Chi-squared test and t-test analysis were used for statistical analysis, and a P-value of < 0.05 was considered significant.

RESULTS: A total of 482 patients received IVIG in Hospital Kuala Lumpur. There were 243 (50.4%) females and 228 (47.3%) males with median age of the patients was 27 years old. The highest indications for IVIG among all patients were hypogammaglobulinemia and other deficiency states in 127 patients (26.3%). The most common indication for one-off treatment in adults was hypogammaglobulinemia and other deficiency states, 35%; whereas in paediatrics, it was Kawasaki disease, 20.3%. The highest indication for regular therapy among adult patients was chronic inflammatory demyelinating polyneuropathy (23.4%), while in paediatrics it was sepsis (31.1%). The clinical category was associated with the frequency status of IVIG usage in both adult and paediatric cohorts with P = 0.004 and P = 0.017, respectively.

CONCLUSION: There were significant differences between the indication of one-off treatment and regular therapy among adult and paediatric patients. A national guideline on the prescription of IVIG for patients is instantly needed to help clinicians in prescribing IVIG appropriately.

PMID:37425378 | PMC:PMC10325126 | DOI:10.21315/mjms2023.30.3.10

Pediatr Infect Dis J. 2023 Jul 6. doi: 10.1097/INF.0000000000004046. Online ahead of print.

NO ABSTRACT

PMID:37409798 | DOI:10.1097/INF.0000000000004046

Infect Drug Resist. 2023 Jun 30;16:4265-4271. doi: 10.2147/IDR.S413900. eCollection 2023.

ABSTRACT

Recipients transplanted for bronchiectasis in the context of a primary immune deficiency, such as common variable immunodeficiency, are at a high risk of severe infection in post-transplantation leading to poorer long-term outcomes than other transplant indications. In this report, we present a fatal case due to chronic Pseudomonas aeruginosa bronchopulmonary infection in a lung transplant recipient with common variable immunodeficiency despite successful eradication of an extensively drug-resistant (XDR) strain with IgM/IgA-enriched immunoglobulins and bacteriophage therapy. The fatal evolution despite a drastic adaptation of the immunosuppressive regimen and the maximal antibiotic therapy strategy raises the question of the contraindication of lung transplantation in such a context of primary immunodeficiency.

PMID:37409241 | PMC:PMC10319284 | DOI:10.2147/IDR.S413900

J Clin Immunol. 2023 Jul 4. doi: 10.1007/s10875-023-01546-z. Online ahead of print.

NO ABSTRACT

PMID:37402930 | DOI:10.1007/s10875-023-01546-z

J Assoc Med Microbiol Infect Dis Can. 2022 Nov 29;7(4):333-342. doi: 10.3138/jammi-2022-0011. eCollection 2022 Nov.

ABSTRACT

BACKGROUND: The rate of breakthrough infection in vaccinated Ontarians during the Omicron wave is unknown.

METHODS: Active participants of the Safety and Efficacy of Preventative COVID Vaccines (STOPCoV) study (892 ≥age 70 years and 369 aged 30-50 years) were invited to participate in a sub-study evaluating breakthrough COVID-19 infection. Self-administered rapid antigen tests (RAT) were reported twice weekly and symptom questionnaires weekly for 6 weeks. The primary outcome was the proportion reporting a positive RAT.

RESULTS: A total of 806 e-consented, and 727 (90%) completed ≥1 RAT, with total 7,116 RATs completed between January 28 and March 29, 2022. Twenty out of twenty-five participants with a positive RAT had a booster vaccine prior to the positive test. All cases were mild, none requiring hospitalization. Nineteen had positive dried blood spot analysis for IgG antibody to the receptor binding domain (RBD) prior to the positive RAT. The mean normalized IgG ratio to RBD was 1.22 (SD 0.29) for younger and 0.98 (SD 0.44) for older participants, values similar to corresponding ratios for those without positive RATs and those in the main cohort. One hundred and five participants reported one and 96 reported ≥2 possible COVID-19 symptoms despite negative RATs. The false negative RAT was low (4% to 6.6 %) compared with subsequent positive nucleoprotein antibody.

CONCLUSIONS: Positive RAT for COVID-19 was infrequent (3.4%). We were unable to determine a protective antibody level against breakthrough infection. Our findings can inform public health COVID-19 restrictions guidelines. Our decentralized study provides a model for rapid institution of new questions during a pandemic.

PMID:37397827 | PMC:PMC10312218 | DOI:10.3138/jammi-2022-0011

Turk J Pediatr. 2023;65(3):536-541. doi: 10.24953/turkjped.2020.1934.

ABSTRACT

BACKGROUND: Hyperimmunoglobulin E syndrome (HIES) due to dedicator of cytokinesis8 (DOCK8) deficiency may present in infancy and childhood with different clinical features involving recurrent infections, allergic dysregulation, and autoimmunity.

CASE: In this report, we describe a patient who first presented with severe hypereosinophilia and went on to develop the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in the context of a severe herpes infection. Investigation revealed the presence of underlying DOCK8 deficiency presenting with atypical clinical features.

CONCLUSIONS: Distinct inflammatory features associated with infections may be seen in the course of primary immunodeficiency diseases, and early functional and molecular genetic tests will aid the proper management.

PMID:37395973 | DOI:10.24953/turkjped.2020.1934

J Allergy Clin Immunol Pract. 2023 Jun 28:S2213-2198(23)00702-X. doi: 10.1016/j.jaip.2023.06.037. Online ahead of print.

ABSTRACT

Cutaneous manifestations are common in patients with inborn errors of immunity (IEI)/primary immunodeficiency (PID) and could be due to infections, immune dysregulation, or lymphoproliferative/malign diseases. Immunologists accept some as warning signs for underlying inborn errors of immunity. Herein, we include noninfectious/infectious cutaneous manifestations that we come across in rare IEI cases in our clinic and provide a comprehensive literature review. For several skin diseases, the diagnosis is challenging and differential diagnosis is necessary. Detailed disease history and examination play a vital role in reaching a diagnosis, especially if there is a potential underlying IEI. A skin biopsy is sometimes necessary, especially if we need to rule out inflammatory, infectious, lymphoproliferative, and malignant conditions. Specific and immunohistochemical stainings are particularly important when diagnosing granuloma, amyloidosis, malignancies, and infections like HHV6, HHV8, HPV, and orf. Elucidation of mechanisms of IEIs has improved our understanding of their relation to cutaneous findings. In challenging cases, the immunological evaluation may lead the approach when there is a specific PID diagnosis or at least help to reduce the number of differential diagnoses. On the other hand, the response to therapy may provide conclusive evidence for some conditions. This review will raise awareness of concomitant lesions and expand the scope of the differential diagnosis of IEI and the spectrum of skin disease therapy by highlighting frequent forms of IEI-associated cutaneous manifestations. The manifestations given here will guide clinicians to plan for alternative use of diverse therapeutics in a multidisciplinary way for skin diseases.

PMID:37391021 | DOI:10.1016/j.jaip.2023.06.037

J Allergy Clin Immunol. 2023 Jun 28:S0091-6749(23)00838-2. doi: 10.1016/j.jaci.2023.06.016. Online ahead of print.

ABSTRACT

BACKGROUND: The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in the TTC7A gene have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics.

OBJECTIVE: This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/PI4KIIIα pathway in the control of leukocytes migration and actin dynamics.

METHODS: Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single cell level.

RESULTS: We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the PI3K/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage and increased cell death in dense 3D gels in the presence of chemokines.

CONCLUSION: Our results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients.

PMID:37390900 | DOI:10.1016/j.jaci.2023.06.016

J Allergy Clin Immunol. 2023 Jun 28:S0091-6749(23)00812-6. doi: 10.1016/j.jaci.2023.06.015. Online ahead of print.

ABSTRACT

BACKGROUND: Activated phosphoinositide-3-kinase (PI3K) δ Syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.

OBJECTIVES: Report the extended spectrum of disease manifestations in APDS1 versus APDS2, compare these to CTLA-4 deficiency, NFκB1 deficiency, and STAT3 gain-of-function (GOF) disease; identify predictors of severity in APDS.

METHODS: Data collection with the European Society for Immunodeficiencies (ESID)-APDS registry. Comparison with published cohorts of the other IEIs.

RESULTS: The analysis of 170 APDS patients outlines high penetrance and early-onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA-4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.

CONCLUSION: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEI is substantial. Some specific features distinguish APDS1 from APDS2. Early-onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.

PMID:37390899 | DOI:10.1016/j.jaci.2023.06.015