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Journal of Clinical Immunology Jan 2022Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined...
Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency with an HLA-matched sibling donor (MSD) or family donor (MFD). Improved overall survival (OS) has been reported compared to the use of unrelated donors, and previous studies have demonstrated that adequate cellular and humoral immune recovery can be achieved even in the absence of conditioning. Detailed insight of the long-term outcome is still limited. We aim to address this by studying a large single-center cohort of 28 adenosine deaminase-deficient patients who underwent a total of 31 HSCT procedures, of which more than half were unconditioned. We report an OS of 85.7% and event-free survival of 71% for the entire cohort, with no statistically significant differences after procedures using related or unrelated HLA-matched donors. We find that donor engraftment in the myeloid compartment is significantly diminished in unconditioned procedures, which typically use a MSD or MFD. This is associated with poor metabolic correction and more frequent failure to discontinue immunoglobulin replacement therapy. Approximately one in four patients receiving an unconditioned procedure required a second procedure, whereas the use of reduced intensity conditioning (RIC) prior to allogeneic transplantation improves the long-term outcome by achieving better myeloid engraftment, humoral immune recovery, and metabolic correction. Further longitudinal studies are needed to optimize future management and guidelines, but our findings support a potential role for the routine use of RIC in most ADA-deficient patients receiving an HLA-identical hematopoietic stem cell transplant, even when a MSD or MFD is available.
Topics: Agammaglobulinemia; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Severe Combined Immunodeficiency; Transplantation Conditioning; Unrelated Donors
PubMed: 34654999
DOI: 10.1007/s10875-021-01145-w -
Iranian Journal of Allergy, Asthma, and... Oct 2023Most patients with X-linked agammaglobulinemia are susceptible to infections, while some cases also suffer from inflammatory or autoimmune complications. We describe a... (Review)
Review
Most patients with X-linked agammaglobulinemia are susceptible to infections, while some cases also suffer from inflammatory or autoimmune complications. We describe a patient with progressive encephalitis who improved after the use of immunomodulatory treatment with corticosteroids, fluoxetine, and nitazoxanide. In most of the cases the evolution of the progressive encephalitis is complicated and catastrophic. Based on our experience and the review of the literature, we propose the use of this combined treatment to control this devastating complication.
Topics: Humans; Genetic Diseases, X-Linked; Encephalitis; Agammaglobulinemia; Combined Modality Therapy
PubMed: 38085151
DOI: 10.18502/ijaai.v22i5.13999 -
Annals of Allergy, Asthma & Immunology... Jul 2017
Topics: Agammaglobulinemia; Bronchiectasis; Humans; Immunoglobulins
PubMed: 28539185
DOI: 10.1016/j.anai.2017.04.020 -
BMC Pediatrics May 2014X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and...
BACKGROUND
X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and circulating mature B cells. It is caused by mutations of the Bruton tyrosine kinase (BTK) gene and is the most common form of inherited antibody deficiency. To our knowledge, this is the first report of XLA from Vietnam.
METHODS
We investigated the BTK gene mutations and clinical features of four unrelated Vietnamese children.
RESULTS
The mean ages at onset and at diagnosis were 2.5 and 8 years, respectively. All patients had a medical history of otitis media, pneumonia, and septicemia at the time of diagnosis. Other infections reported included sinusitis, bronchiectasis, arthritis, skin infections, meningitis, and recurrent diarrhea. We identified one previously reported mutation (c.441G >A) and three novel mutations: two frameshifts (c.1770delG and c.1742 delG), and one nonsense (c.1249A >T).
CONCLUSIONS
The delayed diagnosis may be attributable to insufficient awareness of this rare disease on the background of frequent infections even in the immunocompetent pediatric population in Vietnam. Our results further support the importance of molecular genetic testing in diagnosis of XLA.
Topics: Agammaglobulinaemia Tyrosine Kinase; Agammaglobulinemia; Arthritis; B-Lymphocytes; Bronchiectasis; CD4-CD8 Ratio; Child; Child, Preschool; Codon, Nonsense; Diarrhea; Frameshift Mutation; Genetic Diseases, X-Linked; Humans; Male; Meningitis; Neutropenia; Otitis Media; Pneumonia; Protein-Tyrosine Kinases; Sepsis; Sinusitis; Skin Diseases, Infectious; Vietnam
PubMed: 24885015
DOI: 10.1186/1471-2431-14-129 -
Medicina 2022Antibody deficiencies (AD) are characterized by low or absent immunoglobulin levels or the inability to develop a specific antibody response. They are classified in...
Antibody deficiencies (AD) are characterized by low or absent immunoglobulin levels or the inability to develop a specific antibody response. They are classified in primary (PAD) when there is an intrinsic immune defect, or secondary (SAD) to other diseases or drugs. The aim of our study was to review the evolutio n of AD assisted at the Immunology Unit, Hospital Durand between 1982 and 2020, divided into two periods: Period I (1982-2009) and Period II (2010-2020); to evaluate their growth, epidemiologic features and treatment options. A total of 205 patients were identified, 176 (85.8%) with PAD and 29 (14.2%) with SAD. The most frequent PAD were common variable immunodeficiency in 104 (59%) patients, X linked agammaglobulinemia in 17 (9.6%) and selective IgA deficiency in 26 (14.8%). Genetic defects were found in 25 (14.2%) patients with PAD. SAD cases were associated with rituximab in 21 (72.4%) subjects, haematological disease in three (10.2%) and with antiepileptic drugs in other three; 161 (78.5%) patients were treated with immunoglobulins, 140 (87%) PAD y 21 (13%) SAD; 152 (94.4%) received intravenous immunoglobulins and nine (5.6%) subcutaneous immunoglobulins. Thirty (19.7%) patients treated at first with intravenous immunoglobulins changed to subcutaneous formulations. The increase in number of patients between both periods was greater than 250%, and more than 700% in patients added per year. SAD growth was greater than twice times comparing with PAD. By the end of the study 125 patients continued in follow up, 80% PAD y 20% SAD and 14 died.
Topics: Adult; Agammaglobulinemia; Common Variable Immunodeficiency; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Primary Immunodeficiency Diseases
PubMed: 35639056
DOI: No ID Found -
The Tokai Journal of Experimental and... Jul 2023Bezold's abscess is an extracranial complication of otitis media, in which a cervical abscess forms from the mastoid process through an ostial fistula, and is a rare...
Bezold's abscess is an extracranial complication of otitis media, in which a cervical abscess forms from the mastoid process through an ostial fistula, and is a rare condition in recent years. In this study, we experienced a X-linked agammaglobulinemia, which was discovered due to Bezold's abscess. Case: A 12-year-old boy suffering from recurrent right suppurative otitis media for three months was treated with tympanostomy and oral antibacterial therapy at a local otorhinolaryngology clinic. The patient visited the clinic due to a recurrence of symptoms. CT showed bony defects in the cortical bone and mastoid process of the lateral side of the right mastoid cell. The patient was referred to our hospital, admitted the same day and underwent emergency surgery. Intraoperative findings led to the diagnosis of acute mastoiditis and Bezold's abscess c aused b y mastoiditis spreading to the s ternocleidomastoid muscle. After drainage and administration of ABPC/SBT, the abscess disappeared, and the patient's general condition improved. Subsequently, a blood typing test performed on admission suggested the influence of low immunoglobulin levels. A close examination by the pediatric department led to a diagnosis of X-linked agammaglobulinemia. As a result, the patient receives regular immunoglobulin therapy and has been free of infection, including Bezold's abscess. CONCLUSIONS: In the case of recurrent otitis media and rare infections, congenital immune abnormalities should be considered.
Topics: Male; Child; Humans; Mastoiditis; Abscess; Otitis Media; Agammaglobulinemia
PubMed: 37356973
DOI: No ID Found -
Journal of Translational Medicine May 2019Patients with X-linked agammaglobulinemia (XLA) are protected against invasive bacterial infections due to IgG replacement therapy, but are still at higher risk for...
BACKGROUND
Patients with X-linked agammaglobulinemia (XLA) are protected against invasive bacterial infections due to IgG replacement therapy, but are still at higher risk for mucosal infections of the gut and respiratory tract. This might be explained by to the lack of IgA and IgM, as these antibodies are especially important for protection against invading bacterial pathogens on the mucosal surface.
METHODS
In an attempt to eliminate a chronic norovirus infection in a patient with X-linked agammaglobulinemia, fresh frozen plasma (FFP) was given two times a week for 3 weeks. At each visit, pre- and post-FFP infusion serum and saliva was collected to determine IgG-, IgA- and IgM-concentrations and serum half-life was calculated. Functionality of the immunoglobulins pre- and post-FFP infusion in both serum and saliva was tested by measuring complement activation, agglutination and killing of non-typeable Haemophilus influenzae (NTHi).
RESULTS
Administration of FFP failed to eradicate the chronic norovirus infection. Serum IgA and IgM half-life was 4.2 ± 0.3 and 3.8 ± 0.3 days, respectively. The presence of serum IgM was associated with increased complement binding and complement-mediated killing of NTHi. IgA in saliva was detectable post-FFP and was associated with increased agglutination of NTHi. IgM in saliva was not detectable.
CONCLUSIONS
We conclude that FFP treatment, although ineffective in clearing a chronic norovirus infection in this single patient, might be beneficial to prevent or eliminate bacterial infections in XLA patients by increasing IgM dependent complement-mediated killing in serum and IgA dependent bacterial agglutination on the mucosal surface.
Topics: Agammaglobulinemia; Agglutination; Child, Preschool; Complement C3; Cytotoxicity, Immunologic; Genetic Diseases, X-Linked; Haemophilus influenzae; Humans; Immunoglobulin A; Immunoglobulin M; Male; Plasma; Protein Binding; Saliva; Young Adult
PubMed: 31122289
DOI: 10.1186/s12967-019-1928-x -
Pediatrics Jun 2021Constrictive pericarditis is the final common result of a number of processes that affect the pericardium. Establishing the diagnosis and determining the underlying...
Constrictive pericarditis is the final common result of a number of processes that affect the pericardium. Establishing the diagnosis and determining the underlying etiology of constrictive pericarditis are often a diagnostic rendezvous. Here, we describe a patient who presented to the general practitioner with edema, ascites, and weight gain and was found to have constrictive pericarditis secondary to an inflammatory myofibroblastic tumor of the mediastinum. Interestingly, she had a relative lack of cardiorespiratory complaints, and, aside from the edema and mildly elevated jugular venous pressure, she had an unremarkable cardiac and pulmonary examination. During the diagnostic evaluation for constrictive pericarditis, she was found to have hypogammaglobulinemia and profound lymphocytopenia. A stool α-1-antitrypsin level was sent and was elevated, which confirmed the diagnosis of protein-losing enteropathy, a rare but important complication of constrictive pericarditis. This case highlights important diagnostic considerations and management of these complications for the general practitioner.
Topics: Adolescent; Agammaglobulinemia; Female; Humans; Pericarditis, Constrictive
PubMed: 34049957
DOI: 10.1542/peds.2020-021808 -
Postgraduate Medical Journal May 1991
Topics: Agammaglobulinemia; Female; Gastrointestinal Diseases; Granuloma; Humans; Middle Aged
PubMed: 1852660
DOI: 10.1136/pgmj.67.787.413 -
The Journal of Allergy and Clinical... Feb 2017We present results from clinical studies on plasma infusion done in the late 1970s in patients with hypogammaglobulinemia in which we documented the short half-life of... (Review)
Review
We present results from clinical studies on plasma infusion done in the late 1970s in patients with hypogammaglobulinemia in which we documented the short half-life of both total and allergen-specific IgE in serum. The development of specific allergic sensitization in the skin of those patients followed by the gradual decrease in sensitization over 50 days was also documented. The data are included here along with a discussion of the existing literature about the half-life of IgE in both the circulation and skin. This rostrum reinterprets the earlier clinical studies in light of new insights and mechanisms that could explain the rapid removal of IgE from the circulation. These mechanisms have clinical implications that relate to the increasing use of anti-IgE mAbs for the treatment of allergic disease.
Topics: Agammaglobulinemia; Allergens; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Blood Proteins; Half-Life; Humans; Hypersensitivity; Immunoglobulin E; Immunotherapy; Skin; Treatment Outcome
PubMed: 27496596
DOI: 10.1016/j.jaci.2016.04.056