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Clinical Immunology (Orlando, Fla.) Oct 2022A better understanding of COVID-19 in people with primary immunodeficiency (PI), rare inherited defects in the immune system, is important for protecting this... (Review)
Review
A better understanding of COVID-19 in people with primary immunodeficiency (PI), rare inherited defects in the immune system, is important for protecting this population, especially as population-wide approaches to mitigation change. COVID-19 outcomes in the PI population could have broader public health implications because some people with PI might be more likely to have extended illnesses, which could lead to increased transmission and emergence of variants. We performed a systematic review on COVID-19-associated morbidity and mortality in people with PI. Of the 1114 articles identified through the literature search, we included 68 articles in the review after removing 1046 articles because they were duplicates, did not involve COVID-19, did not involve PI, were not in English, were commentaries, were gene association or gene discovery studies, or could not be accessed. The 68 articles included outcomes for 459 people with PI and COVID-19. Using data from these 459 people, we calculated a case fatality rate of 9%, hospitalization rate of 49%, and oxygen supplementation rate of 29%. Studies have indicated that a number of people with PI showed at least some immune response to COVID-19 vaccination, with responses varying by type of PI and other factors, although vaccine effectiveness against hospitalization was lower in the PI population than in the general population. In addition to being up-to-date on vaccinations, current strategies for optimizing protection for people with PI can include pre-exposure prophylaxis for those eligible and use of therapeutics. Overall, people with PI, when infected, tested positive and showed symptoms for similar lengths of time as the general population. However, a number of people with X-linked agammaglobulinemia (XLA) or other B-cell pathway defects were reported to have prolonged infections, measured by time from first positive SARS-CoV-2 test to first negative test. As prolonged infections might increase the likelihood of genetic variants emerging, SARS-CoV2 isolates from people with PI and extended illness would be good candidates to prioritize for whole genome sequencing.
Topics: COVID-19; COVID-19 Vaccines; Humans; Outcome Assessment, Health Care; RNA, Viral; SARS-CoV-2
PubMed: 35973637
DOI: 10.1016/j.clim.2022.109097 -
Clinical Immunology (Orlando, Fla.) Sep 2021The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. Inhibiting BTK has been hypothesized to ameliorate...
INTRODUCTION
The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe COVID-19, however clinical outcome data is inconclusive.
OBJECTIVE
To evaluate the clinical outcomes of BTK inhibitors (BTKinibs) in patients with COVID-19.
EVIDENCE REVIEW
We searched PubMed, Embase, and Web of Science:Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.
FINDINGS
125 articles were identified, 6 of which met inclusion criteria. The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs.
CONCLUSIONS AND RELEVANCE
BTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration.
PubMed: 34352390
DOI: 10.1016/j.clim.2021.108816 -
The Journal of Allergy and Clinical... Sep 2021X-linked agammaglobulinemia (XLA) is an inherited primary immunodeficiency that usually manifests clinically with recurrent sinopulmonary infections. Gastrointestinal...
BACKGROUND
X-linked agammaglobulinemia (XLA) is an inherited primary immunodeficiency that usually manifests clinically with recurrent sinopulmonary infections. Gastrointestinal manifestations are mostly driven by acute infections and disturbed mucosal immunity, but there is a notable prevalence of inflammatory bowel disease (IBD). Differentiating between XLA-associated enteritis, which can originate from recurrent infections, and IBD can be diagnostically and therapeutically challenging.
OBJECTIVE
This study presents a critical appraisal of the clinical, radiological, endoscopic, and histological features associated with XLA-associated Crohn disease (CD)-like enteritis.
METHODS
We report 3 cases and performed a systematic review of the literature describing the diagnoses and outcomes.
RESULTS
An XLA-related enteropathy presented in adolescence with an ileocolonic CD-like phenotype without perianal disease. Abdominal pain, noninfectious diarrhea, and weight loss were the most common symptoms. Imaging and endoscopic findings closely resemble CD. However, histologically, it presents without nodular lymphoid hyperplasia and only 2 studies reported the presence of granulomas. In addition, in XLA-associated enteritis, immunohistochemistry showed the absence or marked reduction in B cells and plasma cells.
CONCLUSIONS
An XLA-associated enteritis is a distinct pathological process that presents clinically in a manner similar to ileocolonic CD. It is important to evaluate for infectious diarrhea, which is common in XLA and can mimic IBD clinically. Complete multidisciplinary evaluation is, therefore, recommended for XLA patients with persistent gastrointestinal symptoms. Although more research is needed, therapeutic selection for XLA-associated enteritis is like that of IBD, and the possible risk of drug interactions and complications from increasing immunosuppression should be considered.
Topics: Agammaglobulinaemia Tyrosine Kinase; Agammaglobulinemia; Crohn Disease; Enteritis; Genetic Diseases, X-Linked; Humans
PubMed: 34029777
DOI: 10.1016/j.jaip.2021.04.070 -
International Journal of Molecular... Jun 2020Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton's tyrosine kinase (BTK), an enzyme that is crucial in B...
Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton's tyrosine kinase (BTK), an enzyme that is crucial in B cell development. It is FDA approved for the treatment of certain hematological malignancies. Several promising off-target drug effects have led to multiple, mostly preclinical investigations regarding its use in solid tumors. Unfortunately, data on its effectiveness in gynecological malignancies are limited, and (systematic) reviews are missing. The objective of this review was to summarize the existing literature and to analyze the evidence of ibrutinib as a treatment option in gynecological malignancies, including breast cancer. Studies were identified in MEDLINE and EMBASE using a defined search strategy, and preclinical or clinical research projects investigating ibrutinib in connection with these malignancies were considered eligible for inclusion. Our findings showed that preclinical studies generally confirm ibrutinib's efficacy in cell lines and animal models of ovarian, breast, and endometrial cancer. Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response. These mechanisms were elaborated and discussed in the context of the evidence available. Further research is needed in order to transfer the preclinical results to a broader clinical appliance.
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Female; Genital Neoplasms, Female; Humans; Piperidines; Xenograft Model Antitumor Assays
PubMed: 32532074
DOI: 10.3390/ijms21114154 -
Chinese Medical Journal Jul 2017Good's syndrome (GS) is a rare disease characterized by thymoma, hypogammaglobulinemia, low or absent B-cells, decreased T-cells, an inverted CD4+/CD8+ T-cell ratio and... (Review)
Review
BACKGROUND
Good's syndrome (GS) is a rare disease characterized by thymoma, hypogammaglobulinemia, low or absent B-cells, decreased T-cells, an inverted CD4+/CD8+ T-cell ratio and reduced T-cell mitogen proliferative responses. GS is difficult to diagnose preoperatively due to its rarity and lack of typical symptoms, the characteristics of Chinese GS patients are still lacking. This study aimed to systematically review all the clinical, laboratory, and immunologic findings of reported cases of Chinese patients with GS.
METHODS
We searched for case reports and articles up to January 2017 using PubMed, China National Knowledge Infrastructure, Wangfang database and China Science and Technology Journal Database with the following words in combinations as key words: "thymoma," "hypogammaglobulinemia," and "Good's syndrome." The text words and MeSH terms were entered depending on the databases characteristics. The reference lists from retrieved articles were also screened for additional applicable studies. The authors were restricted to Chinese. There was no language restriction.
RESULTS
Forty-seven patients were reported in 27 studies. We found that GS has a nationwide distribution and that most cases (83%) have been described on the mainland of China. The initial clinical presentation is varied, ranging from symptoms related to the thymoma to infections resulting from immunodeficiency. Type AB (50%) is the most common histologic type of thymomas in Chinese GS patients according to the World Health Organization classification of thymomas. With respect to infection, sinopulmonary infection (74%) is the most common type, followed by skin infection (10%) and intestinal tract infection (10%). Diarrhea was presented in 36% of patients, and autoimmune manifestations were presented in 36% of patients.
CONCLUSIONS
GS is a rare association of thymoma and immunodeficiency with a poor prognosis. Astute clinical acumen and increased awareness of the clinical and immunological profile of GS are needed to increase early diagnosis, that would benefit improved therapeutic effects.
Topics: Agammaglobulinemia; Animals; China; Humans; Immunologic Deficiency Syndromes; Rare Diseases; Thymoma; Thymus Neoplasms
PubMed: 28639577
DOI: 10.4103/0366-6999.208234 -
Blood Jul 2016
Meta-Analysis Review
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Atrial Fibrillation; Humans; Incidence; Leukemia; Lymphoma; Piperidines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines
PubMed: 27247135
DOI: 10.1182/blood-2016-05-712828