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Expert Rev Clin Immunol. 2023 Jan 27. doi: 10.1080/1744666X.2023.2174105. Online ahead of print.

ABSTRACT

INTRODUCTION: Genetic defects affect the manner of the immune system’s development, activation, and function. nuclear factor-kappa B subunit 1 (NF-κB1) and NF-κB2 are involved in different biological processes, and deficiency in these transcription factors may reveal clinical and immunological difficulties.

AREAS COVERED: This review article gathers the most frequent clinical and immunological remarkable characteristics of NF-κB1 and NF-κB2 deficiencies. Afterward, make an effort to describe the biological mechanism, which is likely to be the cause of these clinical and immunological abnormalities.

EXPERT OPINION: The present review article has explained the mechanism of contributions of the NF-κB1 and NF-κB2 deficiency in revealing immunodeficiency symptoms, specifically immunological and clinical manifestations. These mechanisms demonstrate the importance of NF-κB1 and NF-κB2 signaling pathways for B and T cell development, activation, antibody production, and immunotolerance. Although, the manifestation of a mutation can range from no symptoms to severe complications in a family.

PMID:36706462 | DOI:10.1080/1744666X.2023.2174105

Arch Argent Pediatr. 2023 Feb 2:e202202804. doi: 10.5546/aap.2022-02804.eng. Online ahead of print.

ABSTRACT

Chronic granulomatous disease is a rare primary immunodeficiency characterized by defects in one of the subunits of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex, which causes a deficiency in the capacity of phagocytes to generate superoxide anion. Within this group, the X-linked form is the most frequent. Here we report the case of a 2-year-old female patient with autosomal recessive chronic granulomatous disease, with a mutation in the CYBA gene, whose initial manifestation was brain abscesses caused by an opportunistic microorganism (Dermacoccus nishinomiyaensis). The infection led to an early diagnostic suspicion, so treatment and prophylaxis were administered in a timely manner. Currently, she is infectionfree, awaiting hematopoietic progenitor cell transplantation. .

PMID:36705996 | DOI:10.5546/aap.2022-02804.eng

Front Pediatr. 2023 Jan 10;10:1099305. doi: 10.3389/fped.2022.1099305. eCollection 2022.

ABSTRACT

BACKGROUND: Nephrotoxicity is the most frequent serious adverse effect associated with amphotericin B deoxycholate treatment, for this reason, in recent years it has been relegated from routine clinical practice and replaced by the new liposomal formulations that have less nephrotoxicity. Nevertheless, dyselectrolytemia are a frequent adverse effect of the use of liposomal amphotericin B that usually are resolved with the withdrawal of the drug.

CASE PRESENTATION: We present a preterm neonate of 25 weeks gestation, with preserved renal function and most electrolytes within normal limits for gestational age except for mild hyponatremia in the first month of life. Due to an infection of the central nervous system and growth of Candida albicans, he required treatment with endovenous liposomal amphotericin B as well as intrathecal amphotericin B deoxycholate showing severe hydroelectrolyte disturbances and clinical worsening compatible with possible tubulopathy showing hypokalemia and severe hyponatremia a few days after starting treatment that persisted over time even after withdrawal of both drugs. Subsequently to the main alterations described, hypomagnesemia, hypophosphatemia, glycosuria and tubular proteinuria were also observed. Calcium levels remained stable after amphotericin B administration and did not require supplementation. In preterm or low birth weight newborns who present unjustified, severe and difficult to correct hydroelectrolyte disturbances despite the usual treatment, a possible tubulopathy should be considered, whether hereditary, primary or secondary to toxins or drugs.

WHAT IS NEW AND CONCLUSION: We present the first case reported in a neonate in whom dyselectrolithemia has been maintained over time after withdrawal of liposomal amphotericin B.

PMID:36704126 | PMC:PMC9871557 | DOI:10.3389/fped.2022.1099305

Front Immunol. 2023 Jan 10;13:1130418. doi: 10.3389/fimmu.2022.1130418. eCollection 2022.

NO ABSTRACT

PMID:36703966 | PMC:PMC9872137 | DOI:10.3389/fimmu.2022.1130418

Clin Case Rep. 2023 Jan 23;11(1):e6776. doi: 10.1002/ccr3.6776. eCollection 2023 Jan.

ABSTRACT

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. We present a 22-year-old Caucasian woman with CVID and granulomatous lymphocytic interstitial lung disease who contracted COVID-19 and was successfully treated with sotrovimab and molnupiravir. This treatment may have contributed to the relatively mild disease course of COVID-19 in our patient.

PMID:36703774 | PMC:PMC9871406 | DOI:10.1002/ccr3.6776

Arch Argent Pediatr. 2023 Feb 1;121(1):e202202885. doi: 10.5546/aap.2022-02885.

ABSTRACT

Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert..

PMID:36701243 | DOI:10.5546/aap.2022-02885

J Thromb Haemost. 2023 Jan;21(1):180-182. doi: 10.1016/j.jtha.2022.10.011.

NO ABSTRACT

PMID:36695383 | DOI:10.1016/j.jtha.2022.10.011

J Thromb Haemost. 2023 Jan;21(1):179. doi: 10.1016/j.jtha.2022.10.018.

NO ABSTRACT

PMID:36695381 | DOI:10.1016/j.jtha.2022.10.018

Med Sci (Paris). 2023 Jan;39(1):23-30. doi: 10.1051/medsci/2022192. Epub 2023 Jan 24.

ABSTRACT

CXCR4 is a chemokine receptor that plays a central role in cell migration but also in other essential processes such as the development of the immune system. Together with its ligand, the chemokine CXCL12, this signalling axis plays an important role in B lymphocyte biology from their early differentiation in the bone marrow to their activation and differentiation into antibody secreting cells, also called plasma cells. Gain-of-function mutations of CXCR4 are found in a rare immunodeficiency, the WHIM Syndrome. These mutations affect the desensitization of the receptor and lead to a gain of function in response to CXCL12. This review summarizes the role of CXCR4 in the humoral immune responses and using the WHIM Syndrome as a paradigm, highlights the critical regulatory role of CXCR4 desensitization in these processes. Indeed, recent works report that fine-tuning of CXCR4 signalling is essential to limit the extra-follicular immune response and support long term antibody-mediated protection.

PMID:36692314 | DOI:10.1051/medsci/2022192

Front Pediatr. 2023 Jan 9;10:1055091. doi: 10.3389/fped.2022.1055091. eCollection 2022.

ABSTRACT

Over the last decades, Inborn Errors of Immunity (IEI) characterized by an immune dysregulatory picture, isolated or combined with infections, have been increasingly identified and referred as Primary Immune Regulatory Disorders (PIRD). PIRD diagnosis may be difficult due to heterogeneity of time onset, sequence of clinical manifestations and laboratory abnormalities. Moreover, the dissection of a PIRD vs. a secondary immunodeficiency (SID) might be a real challenge since the same indications for immunosuppressant treatments might represent per se a PIRD clinical expression. Here we report a female patient with a history of recurrent respiratory and urinary tract infections since early infancy and a diagnosis of Rheumatoid Arthritis in adulthood. After poor response to several biologicals she was treated with Rituximab and sent to immunology referral for a severe hypogammaglobulinemia. Clinical and immunological features matched a diagnosis of common variable immunodeficiency and when IgG replacement therapy and antibiotic prophylaxis were added a good infectious control was obtained. Next generation sequencing analysis has revealed a novel heterozygous VUS in the IKBKB gene (c.1465A > G; p.Ser489Gly). Functional analysis has shown a reduced capacity of B lymphocytes and CD4 positive T cells in inducing IκBα degradation, with negative impact on NF-kB pathway. Due to recurrent infections attributed to a common condition in childhood and to an exclusive autoimmunity-centered approach in adulthood, both diagnosis and suitable treatment strategies have suffered a significant delay. To reduce the diagnostic delay, pediatricians, general practitioners and specialists should be aware of IEI and the challenges to differentiate them from SID. Furthermore, genetic characterization and functional analysis may contribute to a personalized approach, in a perspective of targeted or semi-targeted therapy.

PMID:36699297 | PMC:PMC9869371 | DOI:10.3389/fped.2022.1055091