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Am J Case Rep. 2022 Feb 20;23:e934003. doi: 10.12659/AJCR.934003.

ABSTRACT

BACKGROUND Common variable immunodeficiency (CVID) is a rare disease. Infectious mononucleosis-like symptoms due to Epstein-Barr virus reactivation in adulthood are also rare. Here, we aimed to report a case of Epstein-Barr virus reactivation presenting with relapsing infectious mononucleosis-like symptoms with liver failure in common variable immunodeficiency with chronic hepatitis B virus infection. CASE REPORT A 36-year-old Japanese woman with chronic hepatitis B virus infection developed relapsing fever, lymphadenopathy with marked splenomegaly, and ascites 6 months after treatment with propagermanium, a nonspecific immune modulator, and subsequent treatment with entecavir and pegylated interferon sequential therapy. Although the hepatitis B virus load was controlled, Epstein-Barr virus deoxyribose nucleic acid was detected in her serum. Seven months later, her symptoms improved following corticosteroid treatment. Prior to sequential therapy, she developed pneumonia 4 times in 2 months and exhibited consistent hypoimmunoglobulinemia before corticosteroid treatment. Further examinations showed low amounts of switched memory B cells, and absence or barely detectable levels of isohemagglutinins. Subsequently, she was diagnosed with common variable immunodeficiency. CONCLUSIONS Epstein-Barr virus reactivation with relapsing infectious mononucleosis-like symptoms can occur following immune modulation therapy in patients with common variable immunodeficiency, and this can affect the patient’s primary disease. Therefore, immunoglobulin screening along with the consideration of CVID in all patients is required before immune modulation therapy is planned.

PMID:35184129 | DOI:10.12659/AJCR.934003

Hum Genet. 2022 Feb 19. doi: 10.1007/s00439-021-02400-1. Online ahead of print.

ABSTRACT

Mutations in the X-linked gene MAGT1 cause a Congenital Disorder of Glycosylation (CDG), with two distinct clinical phenotypes: a primary immunodeficiency (XMEN disorder) versus intellectual and developmental disability. It was previously established that MAGT1 deficiency abolishes steady-state expression of the immune response protein NKG2D (encoded by KLRK1) in lymphocytes. Here, we show that the reduced steady-state levels of NKG2D are caused by hypoglycosylation of the protein and we pinpoint the exact site that is underglycosylated in MAGT1-deficient patients. Furthermore, we challenge the possibility that supplementation with magnesium restores NKG2D levels and show that the addition of this ion does not significantly improve NKG2D steady-state expression nor does it rescue the hypoglycosylation defect in CRISPR-engineered human cell lines. Moreover, magnesium supplementation of an XMEN patient did not result in restoration of NKG2D expression on the cell surface of lymphocytes. In summary, we demonstrate that in MAGT1-deficient patients, the lack of NKG2D is caused by hypoglycosylation, further elucidating the pathophysiology of XMEN/MAGT1-CDG.

PMID:35182234 | DOI:10.1007/s00439-021-02400-1

Pediatr Allergy Immunol Pulmonol. 2022 Feb 18. doi: 10.1089/ped.2021.0081. Online ahead of print.

ABSTRACT

Background: COVID-19 has affected humanity not only physically but also mentally. It was expected to have impact on high-risk groups such as the immunocompromised patients and parents/caregivers of them. Our study was aimed to investigate the COVID-19related anxiety, post-traumatic stress levels, and sleep-related parameters of the parents of children with primary immunodeficiency. Methods: Parents of children with primary immunodeficiency and age and gender-matched control group completed questionnaires. Results: Anxiety and post-traumatic stress levels of the study group were found to be significantly higher than the control group. Furthermore, sleep time of the study group was significantly lower than the control group. The subjective sleep quality of the study group was also lower in the study group, but the difference did not reach a significant level. Conclusions: In the ongoing and other possible pandemic processes, professional support for the parents of these children is of great importance.

PMID:35180363 | DOI:10.1089/ped.2021.0081

J Allergy Clin Immunol. 2022 Feb 14:S0091-6749(22)00152-X. doi: 10.1016/j.jaci.2022.01.025. Online ahead of print.

ABSTRACT

Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the HG is secondary or primary is important as this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential causal etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (e.g., discontinuation of an offending drug) or treatment of the underlying condition (e.g., management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy, although data are limited. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, post-transplant, protein-losing) associated with SHG and highlights key areas for future investigation.

PMID:35176351 | DOI:10.1016/j.jaci.2022.01.025

Blood Transfus. 2022 Feb 1. doi: 10.2450/2022.0258-21. Online ahead of print.

ABSTRACT

BACKGROUND: In a context of secondary immunodeficiency, hepatitis E virus (HEV) infection can be responsible for chronic liver disease.

MATERIALS AND METHODS: We investigated HEV infection in patients with primary immunodeficiency treated (or not) with immunoglobulin (Ig) replacement therapy (IgRT) in France, a country with a high seroprevalence of HEV. In a nationwide study of individuals with primary immunodeficiency, 533 patients (349 and 184 receiving IgRT or not, respectively) were tested for HEV RNA and anti-HEV antibodies. In addition, 23 batches of five different commercially available immunoglobulin preparations were screened for anti-HEV IgG.

RESULTS: Three of the 533 patients displayed markers of a recent HEV infection (HEV RNA in one case, and anti-HEV IgG and IgM in two) but no evidence of chronic liver disease. The overall seroprevalence of HEV was 50% (266 out of 533), with values of 68% and 16% in patients receiving IgRT or not, respectively (p<0.001). Anti-HEV IgG were detected in all batches of immunoglobulin preparations, although the titer varied from 3 to 127 IU/g IgG. Seroconversion was observed in 15 of the 22 (68%) patients tested before and after IgRT.

DISCUSSION: No cases of chronic HEV-related disease were detected among patients with primary immunodeficiency and hypogammaglobulinemia, whether they received IgRT or not. This confirms that patients with primary immunodeficiency have a low risk of chronic infection despite a seroprevalence close to that observed in the French general population and that IgRT, which confers a high HEV seroprevalence, might play a key role in protection against chronic infection.

PMID:35175187 | DOI:10.2450/2022.0258-21

J Clin Immunol. 2022 Feb 16. doi: 10.1007/s10875-022-01219-3. Online ahead of print.

NO ABSTRACT

PMID:35174440 | DOI:10.1007/s10875-022-01219-3

Front Immunol. 2022 Jan 31;13:837243. doi: 10.3389/fimmu.2022.837243. eCollection 2022.

ABSTRACT

PURPOSE: Inborn Errors of Immunity (IEI) are heterogeneous disorders of immunity with variable clinical presentation and outcome. This is the first comprehensive report from the United Arab Emirates aiming to describe the demographics, clinical characteristics, categories, treatment modalities and outcome of patients with IEI.

METHODS: This retrospective study was conducted on patients who attended Tawam Hospital between 2016-2020.

RESULTS: We identified 162 patients with IEI, of whom 152 were children. The age of onset of symptoms ranged between birth to 38 years. About two-thirds of patients were Emirati nationals, 64.2% had consanguineous parents and 38.3% of cases were familial. Patients were classified as; immunodeficiencies affecting cellular and humoral immunity (20.4%), combined immunodeficiencies with associated or syndromic features (38.3%), predominantly antibody deficiencies (16%), immune dysregulation (4.3%), congenital defects of phagocytes number or function (8.6%), defects in intrinsic and innate immunity (1.9%) autoinflammatory disorders (1.9%), complement deficiency (6.2%), bone marrow failure (1.9%) and phenocopies of inborn errors of immunity (0.6%). Genetic testing was performed in 85.2% of patients with a diagnostic yield of 92.7%. Complications included bronchiectasis, neoplasia, and vaccine-related infections. Immunoglobulin therapy and antimicrobial prophylaxis were both used in (51.9%) of patients while (20.4%) underwent hematopoietic stem cell transplantation (HSCT). The overall mortality rate was 10.5%.

CONCLUSION: This report highlights the burden of IEI in the UAE. Ongoing education of physicians, establishment of a national registry and considering changes to early BCG vaccination are measures recommended to improve outcomes.

PMID:35173743 | PMC:PMC8841332 | DOI:10.3389/fimmu.2022.837243

J Rheumatol. 2022 Feb 15:jrheum.210850. doi: 10.3899/jrheum.210850. Online ahead of print.

ABSTRACT

Multisystem inflammatory syndrome in adults is a rare postinfectious complication, initially reported in children developing features of Kawasaki disease and toxic shock syndrome after a SARS-CoV-2 infection. Subsequently, the clinical spectrum of the condition was recognized to be broader, defined as an inappropriate systemic inflammatory response with multiorgan dysfunction involving the skin, mucous membranes, and the heart, among other organ systems.

PMID:35169048 | DOI:10.3899/jrheum.210850

Expert Rev Hematol. 2022 Feb 16. doi: 10.1080/17474086.2022.2042246. Online ahead of print.

ABSTRACT

OBJECTIVES: In chronic lymphocytic leukemia (CLL), therapy-related cytotoxicity and the resulting immunodeficiency are thought to contribute to the development of secondary primary malignancies (SPM). Here we analyzed clinical trial data on the occurrence of SPM following chemo-immunotherapy (CIT) regimens in treatment-naïve CLL patients.

METHODS: A systematic literature search was conducted covering multiple databases between 2003-2019. Data from relevant clinical trials on the proportion of patients with SPMs were extracted. Then the number of SPM patients/person-years was calculated by taking into account the trials’ follow-up time. Finally, a random-effects meta-analysis to pool the rates from individual studies was performed.

RESULTS: We identified 22 studies reporting SPM data available for analysis. Random-effects meta-analysis estimated that the number of SPM patients/1000 person-years was 24 (95%CI: 19-29). Results from trials with cancer-specific data indicated 19 (95%CI: 14-26) solid and 9 (95%CI: 6-12) hematological SPM patients/1000 person-years. These estimations did not change significantly when sub-groups were analysed by CIT regimens.

CONCLUSION: Although pooling data with the intention to analyze adverse event rates is challenging, our study concluded that in case of CIT regimens, SPM should be considered an important adverse outcome. Different regimens showed similar trends; however, other clinical and demographic factors have a profound impact in this respect.

PMID:35168449 | DOI:10.1080/17474086.2022.2042246

Cureus. 2022 Jan 12;14(1):e21140. doi: 10.7759/cureus.21140. eCollection 2022 Jan.

ABSTRACT

Background Primary immunodeficiencies are a heterogeneous group of genetic diseases caused by one or more abnormalities in the immune system. Although pulmonary complications are common in patients with primary immunodeficiency diseases, these complications contribute significantly to morbidity and mortality. Aim The aim of our study was to evaluate the distribution of the features of pulmonary radiological involvement and demographic findings in this patient group. Materials and methods The files of patients who were treated and followed up with the diagnosis of primary immunodeficiency between 2014 and 2021 were analyzed retrospectively. Demographic data, symptoms, additional diseases, and computed tomography findings of the patients were recorded. Results The mean age of 32 cases was 37.34±13.54 (20-69) and the age of diagnosis was 28.90±15.75 (1-62). Twenty of the cases were male and 10 were female. The most common symptom was diarrhea with 53.1% and cough with 34.4%. The most common radiological finding is bronchiectasis in 75% of cases. Twenty-one (65.6%) of the cases had recurrent pneumonia before diagnosis and no pneumonia was observed after intravenous ımmunoglobulin replacement therapy. Three of the cases (9.4%) died during the follow-up. Conclusions Primary immunodeficiency should be considered in patients with bronchiectasis and a history of recurrent pneumonia, and further investigations should be performed. Early diagnosis of patients with primary immunodeficiency is very important for the early detection and treatment of malignancy and the interstitial lung disease that may develop.

PMID:35165591 | PMC:PMC8831950 | DOI:10.7759/cureus.21140