Manish Butte

Cureus. 2022 Jun 2;14(6):e25594. doi: 10.7759/cureus.25594. eCollection 2022 Jun.

ABSTRACT

Common variable immunodeficiency (CVID) or acquired hypogammaglobulinemia is one of the common forms of primary immunodeficiency, which primarily affects the respiratory tract, but is often associated with gastrointestinal complications. The pathophysiology is not fully understood, making a diagnosis of CVID difficult. The low levels of IgG and IgA and defective B cells make intravenous immunoglobulin (IVIG) therapy the mainstay of management. The present article describes the journey of a 41-year-old male suffering from CVID and severe recurrent uncontrollable gastrointestinal infections requiring Intravenous immunoglobulin therapy, which was successfully substituted with an alternative oral Hyperimmune Bovine Colostrum and Zinc combination for long term gastrointestinal disease control in a more affordable manner. Keywords: Common variable immunodeficiency, Hypogammaglobulinemia, Primary Immunodeficiency, Gastrointestinal infection, Intravenous Immunoglobulin Therapy, Bovine Colostrum.

PMID:35664290 | PMC:PMC9161369 | DOI:10.7759/cureus.25594

Transfusion. 2022 Jun 4. doi: 10.1111/trf.16938. Online ahead of print.

ABSTRACT

BACKGROUND: Studies evaluating long-term trends of intravenous immunoglobulin (IVIG) titers against microorganisms such as bacteria and fungi have not been conducted. We herein evaluated long-term trends of titers of IVIG lots manufactured from 1998 to 2018, derived from donors in Japan, against microorganisms affecting patients with primary or secondary immunodeficiency diseases.

STUDY DESIGN AND METHODS: Titers against four strains of Pseudomonas aeruginosa, three strains of Staphylococcus aureus, four strains of Haemophilus influenzae, two strains of Klebsiella pneumoniae, one strain of Streptococcus pneumoniae, Enterococcus faecium, Bordetella pertussis, Serratia marcescens, and Candida albicans, were tested immediately after lot release in a commercial clinical testing facility in 1998. The long-term (whole period) and short-term (first and second half of the period) trends of titers were evaluated using regression analysis.

RESULTS: The IVIG lots indicated meaningful titers against all microorganisms that were stable in the short term. The long-term trends could be categorized into stable, slightly decreasing, or decreasing trends, except for the metallo-β-lactamase-producing K. pneumoniae, which indicated a slight increase. Notably, three strains of P. aeruginosa showed remarkable decreasing long-term trends in the titer.

DISCUSSION: Some titers indicate decreasing trends against microorganisms over the long-term, however, is not clear whether the phenomenon diminishes the performance of IVIG. The titers of the IVIG lots could provide helpful information to optimize replacement therapy, such as considering trough values based on the titers in the patient plasma. Therefore, continuous monitoring of IVIG titers against microorganisms is important to understand titer fluctuation and epidemiological background.

PMID:35661368 | DOI:10.1111/trf.16938

Stem Cell Res. 2022 May 31;62:102822. doi: 10.1016/j.scr.2022.102822. Online ahead of print.

ABSTRACT

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a rare autosomal dominant primary immunodeficiency disease (PID) which was caused by the acquired mutation of PIK3CD gene. In this study, we generated a human induced pluripotent stem cell (hiPSC) line CHCMUi001-A from the peripheral blood mononuclear cells (PBMCs) of a APDS patient, who has a heterozygous mutation (c.3061 G > A) in the PIK3CD gene. This iPSC line presented a normal karyotype and exhibited characteristics of pluripotent stem cells. This iPSC line can be very useful for not only studying disease mechanisms but also developing new potential clinical treatments for APDS patients.

PMID:35660815 | DOI:10.1016/j.scr.2022.102822

Sci Immunol. 2022 Jun 3;7(72):eabn2888. doi: 10.1126/sciimmunol.abn2888. Epub 2022 Jun 3.

ABSTRACT

The SKIV2L RNA exosome is an evolutionarily conserved RNA degradation complex in the eukaryotes. Mutations in the SKIV2L gene are associated with a severe inherited disorder, trichohepatoenteric syndrome (THES), with multisystem involvement but unknown disease mechanism. Here, we reported a THES patient with SKIV2L mutations showing severe primary B cell immunodeficiency, hypogammaglobulinemia, and kappa-restricted plasma cell dyscrasia but normal T cell and NK cell function. To corroborate these findings, we made B cell-specific Skiv2l knockout mice (Skiv2l^fl/flCd79a-Cre), which lacked both conventional B-2 and innate-like B-1 B cells in the periphery and secondary lymphoid organs. This was linked to a requirement of SKIV2L RNA exosome activity in the bone marrow during early B cell development at the pro-B cell to large pre-B cell transition. Mechanistically, Skiv2l-deficient pro-B cells exhibited cell cycle arrest and DNA damage. Furthermore, loss of Skiv2l led to substantial out-of-frame V(D)J rearrangement of immunoglobulin heavy chain and severely reduced surface expression of μH, both of which are crucial for pre-BCR signaling and proliferative burst during early B cell development. Together, our data demonstrated a crucial role for SKIV2L RNA exosome in early B cell development in both human and mice by ensuring proper V(D)J recombination and Igh expression, which serves as the molecular basis for immunodeficiency associated with THES.

PMID:35658009 | DOI:10.1126/sciimmunol.abn2888

Allergy Asthma Clin Immunol. 2022 Jun 2;18(1):45. doi: 10.1186/s13223-022-00688-w.

ABSTRACT

BACKGROUND: Human inborn errors of immunity (IEI) are a group of inherited genetic disorders of the immune system. IEI Patients suffer from severe repeated infections, autoimmunity, lymphadenopathy and/or increased susceptibility to malignancies. IEI are due to absence, disproportion, or loss of function of immune cells; mostly inherited in autosomal recessive manner, hence are more common in countries with high rate of consanguinity. Definite diagnosis of IEI is achieved by genetic analysis, however it is not always available.

AIM: to report on different IEI categories and impact of expanding the use of flow cytometry (FCM) in diagnosis, categorization and follow up of IEI patients in a highly consanguineous population.

METHODS: Retrospective chart review on different IEI categories diagnosed at the primary immunodeficiency center in Cairo University Specialized Pediatric hospital from 2011 to 2021 based on expanding the use of FCM.

RESULTS: 1510 IEI patients were diagnosed; 480 were diagnosed genetically with FMF, 11 with cystic fibrosis and 1019 patients were diagnosed with other IEI disorders. Phagocytic defects were the commonest (30%) followed by severe combined immunodeficiency (22%) and combined immunodeficiency (18.3%). FCM testing properly diagnosed and categorized 73% of the cases.

CONCLUSION: Using multi-color FCM to evaluate immune cells populations, subpopulations, functions, and intracellular proteins expression is proved a useful cost-effective method for screening, categorization and follow up of IEI patients. FCM can improve the diagnosis of IEI significantly when tests are properly targeted and well designed. This study presents a 10-year experience in diagnosis of IEI using FCM at a tertiary referral center in a setting of limited resources and yet high prevalence of IEI.

PMID:35655284 | DOI:10.1186/s13223-022-00688-w

Pediatr Pulmonol. 2022 Jun 2. doi: 10.1002/ppul.26027. Online ahead of print.

ABSTRACT

Numerous publications on wheezing disorders in children younger than 6 years have appeared in the medical literature over the last decades with the aim of shedding light on the mechanistic pathways (endotypes) and treatment. Nevertheless, there is yet no consensus as to the appropriate way to manage preschool wheeze mainly because of the lack of a clear definition of “preschool asthma” and the paucity of scientific evidence concerning its underlying endotypes. A symptom-based approach is inadequate since the human airway can respond to external stimuli with a limited range of symptoms and signs, including cough and wheeze, and these manifestations represent the final expression of many clinical entities with potentially different pathophysiologies requiring different individualized treatments. Hence, new studies challenge the symptom-based approach and promote the importance of managing the wheezy child based on the “airway phenotype”. This will enable the clinician to identify not only the child with a serious underlying pathology (e.g. a structural airway disorder or immunodeficiency) who is in need of prompt and specific treatment but also increase the specificity of treatment for the child with symptoms suggestive of an “asthma” syndrome. In the latter case, focus should be given to the identification of treatable traits. This review summarizes the current understanding in management of preschool wheezing and highlights the unmet need for further research. This article is protected by copyright. All rights reserved.

PMID:35652262 | DOI:10.1002/ppul.26027

Clin Rev Allergy Immunol. 2022 Jun 1. doi: 10.1007/s12016-022-08942-0. Online ahead of print.

ABSTRACT

Primary immunodeficiency (PID) may impact any component of the immune system. The number of PID and immune dysregulation disorders is growing steadily with advancing genetic detection methods. These expansive recognition methods have changed the way we characterize PID. While PID were once characterized by their susceptibility to infection, the increase in genetic analysis has elucidated the intertwined relationship between PID and non-infectious manifestations including autoimmunity. The defects permitting opportunistic infections to take hold may also lead the way to the development of autoimmune disease. In some cases, it is the non-infectious complications that may be the presenting sign of PID autoimmune diseases, such as autoimmune cytopenia, enteropathy, endocrinopathies, and arthritis among others, have been reported in PID. While autoimmunity may occur with any PID, this review will look at certain immunodeficiencies most often associated with autoimmunity, as well as their diagnosis and management strategies.

PMID:35648371 | DOI:10.1007/s12016-022-08942-0

Int J Neonatal Screen. 2022 May 10;8(2):33. doi: 10.3390/ijns8020033.

ABSTRACT

Screening for severe combined immunodeficiency (SCID) was added to the New Zealand national newborn screening programme in December 2017. Documentation pertaining to the application to add SCID to the panel and screening results over the first three years were reviewed. Screening evaluation metrics were shown to differ according to site of collection (babies in a neonatal intensive care unit vs. the community), definition of a positive test (out-of-range result vs. result leading to a further action on baby), and screening target/case definition (primary SCID vs. non-SCID T-cell lymphopenia). Our experience demonstrates both the value of close clinical involvement during the implementation phase of SCID screening and that the use of standard definitions will facilitate international comparison.

PMID:35645287 | DOI:10.3390/ijns8020033

Vet Dermatol. 2022 May 29. doi: 10.1111/vde.13097. Online ahead of print.

ABSTRACT

Toxoplasma gondii is a ubiquitous protozoan, for which felids are the definitive host. Immunocompromised individuals are susceptible to recrudescent toxoplasmosis. This case describes a 6-year-old, feline immunodeficiency virus-positive domestic short hair cat with feline atopic skin syndrome that developed fatal toxoplasmosis after treatment with oclacitinib for five months.

PMID:35644925 | DOI:10.1111/vde.13097

Pediatr Dermatol. 2022 May 29. doi: 10.1111/pde.15032. Online ahead of print.

ABSTRACT

Granulomatous skin disease is known to be associated with various primary immunodeficiencies, including ataxia telangiectasia (AT). Recent reports of persistence of live vaccine strain rubella within such cutaneous granulomas have raised concern regarding the safety of vaccination. Here we report a case of cutaneous granuloma in association with AT, demonstrating wild type, rather than vaccine strain rubella. This supports the persistence of rubella as a causative mechanism, but suggests it is not vaccine strain-specific, and thus may impact the decision of those considering not vaccinating this subset of children.

PMID:35644916 | DOI:10.1111/pde.15032