Manish Butte

Dermatol Online J. 2021 Jun 15;27(6). doi: 10.5070/D327654067.

ABSTRACT

A 40-year-old previously healthy, non-atopic woman was referred for evaluation of a possible immunodeficiency disorder in the setting of an unusual erosive cheilitis and history of recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection. Extensive work-up was non-diagnostic, including screening for immunologic disorders. She had failed multiple therapeutic modalities, including corticosteroid and immunosuppressive therapy. Tissue biopsy from the lip proved pivotal in demonstrating changes suggestive of factitial disease. This led to further detailed history-taking, yielding evidence of considerable psychologic distress. The patient was diagnosed with exfoliative cheilitis related to factitial disease in association with underlying untreated anxiety and psychologic trauma.

PMID:34387067 | DOI:10.5070/D327654067

Pediatrics. 2021 Aug 12:e2020035824. doi: 10.1542/peds.2020-035824. Online ahead of print.

ABSTRACT

Neonatal herpes simplex virus encephalitis (HSVE) often results in long-lasting neuro-disability in affected children. In addition to primary HSVE and HSVE relapses, children with herpes simplex virus are at increased risk of developing anti-N-methyl-d-aspartate receptor encephalitis (NMDARe), an autoimmune encephalitis. In this study, we describe a patient with neonatal disseminated herpes infection, who developed HSVE after discontinuation of 2 years of acyclovir suppressive therapy. After resolution of HSVE, the patient rapidly deteriorated with significant behavioral and neurologic changes including emotional outbursts, fearfulness, involuntary movements, and focal seizures. The patient was diagnosed with anti-NMDARe and was later found to have low toll-like receptor-3 function. In this study, we review published pediatric cases of anti-NMDARe after HSVE as well as previous literature and primary data examining the presentation, predisposing risk factors, predictive outcomes, future directions, and the role of immunodeficiency in HSVE-mediated anti-NMDARe. The neonatal immune system and developing brain are disproportionately vulnerable to early viral exposure; therefore, it is important to recognize the value of early immunodeficiency screening in patients with neonatal herpes simplex virus. By understanding the immune landscape within this patient population, we can mitigate long-term neurologic disability and improve the quality of life of affected children.

PMID:34385350 | DOI:10.1542/peds.2020-035824

J Allergy Clin Immunol. 2021 Aug 9:S0091-6749(21)01207-0. doi: 10.1016/j.jaci.2021.07.033. Online ahead of print.

ABSTRACT

BACKGROUND: B cell affinity maturation in germinal center (GC) relies on regulated actin dynamics for cell migration and cell-to-cell communication. Activating mutations in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) cause X-linked neutropenia (XLN) with reduced serum level of IgA.

OBJECTIVE: To investigate the role of B cells in XLN pathogenesis.

METHODS: We examined B cells from six XLN patients of which two have novel R268W and S271F mutations in WASp. By using immunized XLN mouse models that carry the corresponding patient mutations WASp L272P or WASp I296T, we examined the B cell response.

RESULTS: XLN patients had normal naïve B cells and plasmablasts, but reduced IgA⁺ B cells and memory B cells, and poor B cell proliferation. Upon immunization, XLN mice had a 2-fold reduction in germinal center B cells in spleen, however, increased generation of plasmablasts and plasma cells. In vitro, XLN B cells showed reduced Ig class switching and aberrant cell division, and increased production of Ig switched plasma cells.

CONCLUSION: These results show that overactive WASp predisposes B cells for pre-mature differentiation into plasma cells at the expense of cell proliferation and Ig class switching.

PMID:34384840 | DOI:10.1016/j.jaci.2021.07.033

Biomed J. 2021 Apr 19:S2319-4170(21)00038-X. doi: 10.1016/j.bj.2021.04.005. Online ahead of print.

ABSTRACT

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited non-malignant and non-infectious lymphoproliferative syndrome caused by mutations in genes affecting the extrinsic apoptotic pathway (FAS, FASL, CASP10). The resulting FAS-mediated apoptosis defect accounts for the expansion and accumulation of autoreactive (double-negative) T cells leading to cytopenias, splenomegaly, lymphadenopathy, autoimmune disorders, and risk of lymphoma. However, there are other monogenetic disorders known as ALPS-like syndromes that can be clinically similar to ALPS but are genetically and biologically different, such as observed in patients with immune checkpoint deficiencies, particularly cytotoxic T-lymphocyte antigen 4 (CTLA-4) insufficiency and lipopolysaccharide-responsive beige-like anchor protein LRBA deficiency. CTLA-4 insufficiency is caused by heterozygous mutations in CTLA-4, an essential negative immune regulator that is constitutively expressed on regulatory T (Treg) cells. Mutations in CTLA-4 affect CTLA-4 binding to CD80-CD86 costimulatory molecules, CTLA-4 homodimerization, or CTLA-4 intracellular vesicle trafficking upon cell activation. Abnormal CTLA-4 trafficking is also observed in patients with LRBA deficiency, a syndrome caused by biallelic mutations in LRBA that abolishes the LRBA protein expression. Both immune checkpoint deficiencies are biologically characterized by low levels of CTLA-4 protein on the cell surface of Tregs, accounting for the autoimmune manifestations observed in CTLA4-insufficient and LRBA-deficient patients. In addition, both immune checkpoint deficiencies present with an overlapping but heterogeneous clinical picture despite the difference in inheritance and penetrance. In this review, we describe the most prominent clinical features of ALPS, CTLA-4 insufficiency and LRBA deficiency, emphasizing their corresponding biological mechanisms. We also provide some clinical and laboratory approaches to diagnose these three rare immune disorders, together with therapeutic strategies that have worked best at improving prognosis and quality life of patients.

PMID:34384744 | DOI:10.1016/j.bj.2021.04.005

Proteomics. 2021 Aug 12:e2100133. doi: 10.1002/pmic.202100133. Online ahead of print.

ABSTRACT

Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID-19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR-confirmed COVID-19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6-8 and 66 at WHO stages 1-3 COVID-19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha-1-antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID-19. The clinical corollary is that COVID-19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha-1-antitripsin, may represent a valid and effective therapeutic approach in COVID-19, targeting improvement of endothelial integrity. This article is protected by copyright. All rights reserved.

PMID:34383378 | DOI:10.1002/pmic.202100133

BMJ Open. 2021 Aug 11;11(8):e050523. doi: 10.1136/bmjopen-2021-050523.

ABSTRACT

OBJECTIVE: To investigate the psychosocial impact of COVID-19 on Malaysian families.

DESIGN: A cross-sectional study performed using an anonymous online questionnaire distributed through social media, email and the Department of Social Welfare.

SETTING: Malaysian families were invited to answer the questionnaires. The sampling was performed between 12 May 2020 and 9 June 2020.

INTERVENTION: The psychological impact was assessed using the Impact of Event Scale-Revised (IES-R) and Children’s Revised Impact of Event Scale (CRIES). The mental health status was assessed using the Depression, Anxiety and Stress Scale (DASS) 21.

MAIN OUTCOME MEASURE: (1) Psychological impact on Malaysian families. (2) Prevalence of mental health status of Malaysian families during COVID-19 pandemic.

RESULT: A total of 409 Malaysian families have responded (409 parents and 348 children), 154 respondents (38%) reported high psychological impact (score 14) for psychological construct and 189 respondents (46%) reported high psychological impact (score 6) for behavioural construct. A significantly higher proportion of respondents with not permanent employment status of the family lead reported high psychological impact. The prevalence of anxiety reported from family respondents was 23%. Forty-five children answered the DASS-21 questionnaire; 28.5% reported anxiety, 31.4% reported depression and 13.3% reported stress. The job security status of the family lead was found to be the predictive factor for the mean total IES-R score (psychological construct) and ethnicity for mean total CRIES-8 and CRIES-13.

CONCLUSION: Rates of depression and anxiety during the COVID-19 pandemic were high. Findings suggest that urgent measures to ensure job security among Malaysian families are important to reduce the impact of the COVID-19 pandemic on psychosocial and mental health outcomes.

PMID:34380732 | DOI:10.1136/bmjopen-2021-050523

J Infect Chemother. 2021 Aug 7:S1341-321X(21)00212-9. doi: 10.1016/j.jiac.2021.07.023. Online ahead of print.

ABSTRACT

We describe a patient with invasive Haemophilus influenzae type b (Hib) infection despite being completely immunized by a conjugate Hib vaccine. Although Hib vaccination has contributed to significant reduction in invasive Hib infection, there are some case reports of invasive Hib infections despite immunization. Immunoglobulin (Ig) deficiency is the main cause of primary vaccine failure, and IgG2 subclass deficiency is known to be the leading cause. A previously healthy 13-month-old boy visited the outpatient clinic with a 5-day history of fever (40.0 °C), cough, and vomiting, and was diagnosed with bacterial meningitis, purulent pericarditis, and arthritis. Hib was recovered from blood, cerebrospinal fluid, and pericardial fluid. Immunological examination revealed subnormal IgG and IgA titers at 13 and 17 months of age. Serum IgG2 titer was recovered at 17 months of age despite being low at 13 months. Comprehensive gene analysis for primary immunodeficiency syndromes (primary antibody deficiency, common variable immunodeficiency, and toll-like receptor abnormalities) were negative. The antibody titer against Hib [anti-polyribosylribitol phosphate (PRP) antibody] was lower than the long-term protective titer (1.0 μg/ml) at 13 months of age, but was reactively increased to 2.38 μg/mL two months after booster immunization. Transient hypogammaglobulinemia of infancy (THI) is described as an accentuation and prolongation of the physiologic Ig nadir that is normally observed during infancy and defined as low IgG and IgA levels in the first three years of life. We speculate that he developed an invasive Hib infection as a result of primary Hib vaccine failure caused by THI.

PMID:34376350 | DOI:10.1016/j.jiac.2021.07.023

Infect Dis (Lond). 2021 Aug 10:1-6. doi: 10.1080/23744235.2021.1957144. Online ahead of print.

ABSTRACT

BACKGROUND: Manifestations and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well documented in patients with common variable immunodeficiency disorder (CVID).

METHODS: A Danish nationwide retrospective clinician-reported survey.

RESULTS: Eleven patients with CVID and SARS-CoV-2 infection were identified. The median age was 50 years (range 22-72). All were on immunoglobulin replacement therapy. Eight patients had other pre-existing co-morbidities. Three patients were asymptomatic during the SARS-CoV-2 infection while seven developed mild coronavirus disease 2019 (COVID-19). One patient had more severe disease with hypoxia and required oxygen therapy. This patient had multiple co-morbidities including well known risk factors for severe COVID-19. All patients recovered.

CONCLUSIONS: The results suggest that CVID may not be a risk factor for severe COVID-19. However, further monitoring of this immunodeficient population is needed to confirm our observation.

PMID:34375571 | DOI:10.1080/23744235.2021.1957144

Viruses. 2021 Jul 20;13(7):1407. doi: 10.3390/v13071407.

ABSTRACT

The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global polio eradication. However, polio outbreaks, mainly caused by type 2 circulating vaccine-derived poliovirus (cVDPV2), are increasing worldwide. Meanwhile, immunodeficiency-associated vaccine-derived poliovirus (iVDPV) is considered another risk factor during the final stage of global polio eradication. Patients with primary immunodeficiency diseases are associated with higher risks for long-term iVDPV infections. Although a limited number of chronic iVDPV excretors were reported, the recent identification of a chronic type 2 iVDPV (iVDPV2) excretor in the Philippines highlights the potential risk of inapparent iVDPV infection for expanding cVDPV outbreaks. Further research on the genetic characterizations and molecular evolution of iVDPV2, based on comprehensive iVDPV surveillance, will be critical for elucidating the remaining risk of iVDPV2 during the post-OPV era.

PMID:34372613 | DOI:10.3390/v13071407

J Med Virol. 2021 Aug 9. doi: 10.1002/jmv.27257. Online ahead of print.

ABSTRACT

Cytomegalovirus (CMV) is an ubiquitous herpesvirus which develops lifelong latency following primary infection and can be reactivated following immune suppression. CMV encephalopathy has been described in few reports after hematopoietic stem cell transplantation and in patients with acquired immunodeficiency syndrome. To the best of our knowledge, CMV encephalopathy following CAR-T cells infusion had not been previously reported. Initial CMV viral load and monitoring is crucial in patients with CAR-T cells to allow early intervention with aggressive antiviral treatment without delay if needed. This article is protected by copyright. All rights reserved.

PMID:34370316 | DOI:10.1002/jmv.27257