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Brazilian Journal of Anesthesiology... 2020This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned... (Review)
Review
[Update on perioperative hypersensitivity reactions: joint document from the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part II: etiology and diagnosis].
This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned with perioperative anaphylaxis, aims to review the pathophysiological reaction mechanisms, triggering agents (in adults and children), and the approach for diagnosis during and after an episode of anaphylaxis. As anaphylaxis assessment is extensive, the identification of medications, antiseptics and other substances used at each setting, the comprehensive data documentation, and the use of standardized nomenclature are key points for obtaining more consistent epidemiological information on perioperative anaphylaxis.
Topics: Adult; Allergy and Immunology; Anaphylaxis; Anesthesiology; Angioedema; Bradykinin; Brazil; Child; Drug Hypersensitivity; Humans; IgA Deficiency; Immunoglobulin E; In Vitro Techniques; Mastocytosis; Perioperative Period; Preoperative Care; Risk Factors; Skin Tests; Societies, Medical; Symptom Assessment; Terminology as Topic; Vasodilator Agents
PubMed: 33308829
DOI: 10.1016/j.bjan.2020.08.008 -
Journal of Clinical Immunology Feb 2021Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study.
OBJECTIVE
To compare the efficacy of PA and IRT in a randomized crossover trial.
METHODS
A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared.
RESULTS
The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01).
CONCLUSION
We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT.
CLINICAL IMPLICATION
Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.
Topics: Antibiotic Prophylaxis; Child; Female; Humans; IgG Deficiency; Immunoglobulin G; Immunologic Deficiency Syndromes; Male; Middle Aged; Persistent Infection; Primary Immunodeficiency Diseases
PubMed: 33206257
DOI: 10.1007/s10875-020-00841-3 -
BMC Nephrology Nov 2020Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia,... (Review)
Review
Delayed diagnosis of Angioimmunoblast T-cell lymphoma presenting with type II Cryoglobulinemia and acute kidney injury: a case report and narrative review of the literature.
BACKGROUND
Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia, autoantibodies and systemic involvement in AITL has often led to a delay in diagnosis or even misdiagnosis in practice. We herewith present a case of AITL that primarily presented with acute kidney injury associated with type II Cryoglobulinemia, the underlying cause was only identified 8 months after the emergence of initial symptoms.
CASE PRESENTATION
A 67-year old woman presented with 2-month history of intermittent joint pain and a 3-day history of bilateral lower limb edema and acute kidney injury. Initial laboratory investigations showed marked hypocomplementemia with positive autoantibodies of ANA, anti-cardiolipin-IgM and direct antiglobulin. The serum and urinary Immunofixation and serum cryoglobulin tests were negative, while the serum free κ to λ light chain ratio was 0.231. A renal biopsy showed a diffuse proliferative glomerulonephritis with intracapillary pseudothrombi formation. There were orderly arranged microtubular structures of 20-35 nm in diameter in the subendothelial and mesangial area on electron microscopy. Shortly afterwards, the patient developed tingling affecting her finger tips and weak hands and legs. A diagnosis of cryoglobulinemia complicated with cryoglobulinemic glomerulonephritis and polyneuropathy was made. She responded well to methylprednisolone, plasma exchange and rituximab. However, 3 months later, she presented with generalized pruritic rash, weight loss, and inguinal lymphadenopathy. A subsequent inguinal excisional lymph node biopsy at month 8 revealed AITL as the underlying disease.
CONCLUSIONS
AITL and its associated B cell dysregulation can give rise to autoimmunity and cryoglobulinemia which may conceal itself as the underlying disorder. In various clinical scenarios of auto-immune diseases, it is advisable that the clinicians should take into consideration the multi-faceted lymphoma.
Topics: Acute Kidney Injury; Adult; Aged; Blood Chemical Analysis; Complement C3; Creatinine; Cryoglobulinemia; Cryoglobulins; Delayed Diagnosis; Female; Humans; Kidney; Lymphoma, T-Cell; Male; Middle Aged
PubMed: 33160311
DOI: 10.1186/s12882-020-02125-9 -
Immunity Nov 2020Precise targeting of activation-induced cytidine deaminase (AID) to immunoglobulin (Ig) loci promotes antibody class switch recombination (CSR) and somatic hypermutation...
Precise targeting of activation-induced cytidine deaminase (AID) to immunoglobulin (Ig) loci promotes antibody class switch recombination (CSR) and somatic hypermutation (SHM), whereas AID targeting of non-Ig loci can generate oncogenic DNA lesions. Here, we examined the contribution of G-quadruplex (G4) nucleic acid structures to AID targeting in vivo. Mice bearing a mutation in Aicda (AID) that disrupts AID-G4 binding modeled the pathology of hyper-IgM syndrome patients with an orthologous mutation, lacked CSR and SHM, and had broad defects in genome-wide AID chromatin localization. Genome-wide analyses also revealed that wild-type AID localized to MHCII genes, and AID expression correlated with decreased MHCII expression in germinal center B cells and diffuse large B cell lymphoma. Our findings indicate a crucial role for G4 binding in AID targeting and suggest that AID activity may extend beyond Ig loci to regulate the expression of genes relevant to the physiology and pathology of activated B cells.
Topics: Animals; B-Lymphocytes; Chromatin; Computational Biology; Cytidine Deaminase; Disease Models, Animal; Disease Susceptibility; Enzyme Activation; Fluorescent Antibody Technique; G-Quadruplexes; Gene Expression Profiling; Genome-Wide Association Study; Germinal Center; HLA Antigens; Humans; Hyper-IgM Immunodeficiency Syndrome; Immunoglobulin Class Switching; Immunophenotyping; Lymphocyte Activation; Lymphoma, Large B-Cell, Diffuse; Mice; Mice, Transgenic; Mutation
PubMed: 33098766
DOI: 10.1016/j.immuni.2020.10.003 -
Neurology(R) Neuroimmunology &... Nov 2020
Topics: Adolescent; Athetosis; CD40 Ligand; Chorea; Deep Brain Stimulation; Globus Pallidus; Humans; Hyper-IgM Immunodeficiency Syndrome; Magnetic Resonance Imaging; Male
PubMed: 33067350
DOI: 10.1212/NXI.0000000000000899 -
PloS One 2020Adults with IgG subclass deficiency (IgGSD) with subnormal IgG2 are inadequately characterized.
BACKGROUND
Adults with IgG subclass deficiency (IgGSD) with subnormal IgG2 are inadequately characterized.
METHODS
We retrospectively analyzed observations in unrelated adults with IgGSD evaluated in a single hematology clinic (1991-2019) and selected those with subnormal serum IgG2 (<117 mg/dL (<1.2 g/L)) without corticosteroid therapy to describe: age; prevalence of women; upper/lower respiratory infection; autoimmune condition(s); atopy; other allergy; frequent or severe respiratory tract infection in first-degree relatives; IgG, IgG subclasses, IgA, and IgM; blood lymphocyte subpopulations; human leukocyte antigen (HLA)-A and -B types and haplotypes; and 23-valent pneumococcal polysaccharide vaccination (PPSV23) responses. We determined the prevalence of subnormal IgG2 among unrelated adults with IgGSD without corticosteroid therapy and compared general characteristics of those with and without subnormal IgG2.
RESULTS
There were 18 patients (94.4% women) with subnormal IgG2. Mean age was 52 ± 11 y. Upper/lower respiratory infection occurred in 94.4%/74.8%, respectively. Autoimmune condition(s), atopy, other allergy, and frequent or severe respiratory infection in first-degree relatives occurred in 44.4%, 44.4%, 61.1%, and 22.2%, respectively. Median IgG2 was 105 mg/dL (83, 116). Subnormal IgG, IgG1, IgG3, IgG4, IgA, and IgM was observed in 66.7%, 50.0%, 100.0%, 5.6%, 33.3%, and 0%, respectively. Lymphocyte subpopulations were normal in most patients. HLA frequencies were similar in patients and controls. Three of 4 patients had no protective S. pneumoniae serotype-specific IgG levels before or after PPSV23. These 18 patients represent 7.6% of 236 adults with IgGSD. Prevalence of subnormal IgG, subnormal IgG3, and subnormal IgA was significantly greater in 18 adults with subnormal IgG2 than 218 adults without subnormal IgG2. Prevalence of subnormal IgM was significantly lower in patients with subnormal IgG2.
CONCLUSIONS
Characteristics of adults with IgGSD with subnormal IgG2 include female predominance, other immunologic abnormalities, subnormal IgG3 and/or IgG1, lack of HLA-A and -B association, and suboptimal PPSV23 response.
Topics: Adult; Biomarkers; Female; Follow-Up Studies; HLA Antigens; Humans; IgG Deficiency; Immunoglobulin G; Incidence; Lymphocytes; Male; Middle Aged; Prognosis; ROC Curve; Respiratory Tract Infections; Retrospective Studies; Risk Factors
PubMed: 33048985
DOI: 10.1371/journal.pone.0240522 -
Frontiers in Immunology 2020A previously healthy 19-year-old Syrian man presented with atypical and severe mucosal leishmaniasis caused by . During a 2-year period, he had three severe relapses...
A previously healthy 19-year-old Syrian man presented with atypical and severe mucosal leishmaniasis caused by . During a 2-year period, he had three severe relapses despite various treatment strategies, including liposomal amphotericin B and Miltefosine. Because of the unusual clinical presentation, potential underlying immunodeficiency was investigated. Normal T and NK cell counts were found. The B cell count was slightly elevated at 0.7 × 10 cells/L (0.09 × 10 to 0.57 × 10 cells/L), but the proportions of memory and isotype switched memory B cells were severely diminished IgG levels were low, at 309 mg/dL (610-1490 mg/dL). The initial IgM and IgA levels were within normal range, but the IgA levels decreased to 57 mg/dL (70-430 mg/dL) during follow up. Common variable immunodeficiency (CVID) was initially suspected, because the immunological results of low IgG and IgA, low switched memory B cells, no profound T cell deficiency found and absence of secondary cause of hypogammaglobulinemia were compatible with this diagnosis (ESID 2019). However, the highly unusual and severe clinical presentation of is not suggestive of B-cell deficiency or CVID. Eventually a pathogenic nonsense variant in the CD40 ligand gene [p.(Arg11)] was identified by whole genome sequencing, thus enabling the diagnosis of X-linked hyper IgM syndrome. This case illustrates and supports the potential for the use of whole genome sequencing in accurate diagnosis of primary immunodeficiencies.
Topics: Biomarkers; Biopsy; CD40 Ligand; DNA Mutational Analysis; Endoscopy; Humans; Hyper-IgM Immunodeficiency Syndrome; Immunophenotyping; Leishmaniasis; Male; Mucous Membrane; Mutation; Symptom Assessment; Syria; T-Lymphocytes; Whole Genome Sequencing; Young Adult
PubMed: 33013931
DOI: 10.3389/fimmu.2020.567856 -
Mucosal Immunology Mar 2021Although activation of adaptive immunity is a common pathological feature of chronic obstructive pulmonary disease (COPD), particularly during later stages of the...
Although activation of adaptive immunity is a common pathological feature of chronic obstructive pulmonary disease (COPD), particularly during later stages of the disease, the underlying mechanisms are poorly understood. In small airways of COPD patients, we found that localized disruption of the secretory immunoglobulin A (SIgA)-containing mucosal immunobarrier correlated with lymphocyte accumulation in airway walls and development of tertiary lymphoid structures (TLS) around small airways. In SIgA-deficient mice, we observed bacterial invasion into the airway epithelial barrier with lymphocytic infiltration and TLS formation, which correlated with the progression of COPD-like pathology with advanced age. Depletion of either CD4 or CD8 T lymphocytes reduced the severity of emphysema in SIgA-deficient mice, indicating that adaptive immune activation contributes to progressive lung destruction. Further studies revealed that lymphocyte infiltration into the lungs of SIgA-deficient mice was dependent on monocyte-derived dendritic cells (moDCs), which were recruited through a CCR2-dependent mechanism in response to airway bacteria. Consistent with these results, we found that moDCs were increased in lungs of COPD patients, along with CD4 and CD8 effector memory T cells. Together, these data indicate that endogenous bacteria in SIgA-deficient airways orchestrate a persistent and pathologic T lymphocyte response through monocyte recruitment and moDC differentiation.
Topics: Adaptive Immunity; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells, Cultured; Dendritic Cells; Emphysema; Female; Gene Knockout Techniques; Humans; IgA Deficiency; Immunoglobulin A; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Monocytes; Pulmonary Disease, Chronic Obstructive; Receptors, CCR2; Tertiary Lymphoid Structures
PubMed: 32968197
DOI: 10.1038/s41385-020-00344-9 -
Brain & Development Feb 2021Bell's palsy is an acute facial paralysis with known association to viral infections. We describe a medically complex 6-year-old male with hyper IgM syndrome who...
Bell's palsy is an acute facial paralysis with known association to viral infections. We describe a medically complex 6-year-old male with hyper IgM syndrome who presented with unilateral facial droop and positive SARS-CoV-2 RT-PCR. This is the first reported pediatric case of Bell's palsy in the setting of SARS-CoV-2 infection.
Topics: Abnormalities, Multiple; Acyclovir; Antiviral Agents; Asthma; Bell Palsy; COVID-19; Child; Cleft Palate; Gastrostomy; Glucocorticoids; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Hyper-IgM Immunodeficiency Syndrome; Hypospadias; Immunoglobulins, Intravenous; Immunologic Factors; Male; Prednisolone; SARS-CoV-2; Sleep Apnea, Obstructive
PubMed: 32950319
DOI: 10.1016/j.braindev.2020.08.017 -
Case Reports in Immunology 2020X-linked lymphoproliferative disease (XLP1) is a rare primary immunodeficiency characterized by EBV-triggered immune dysregulation, lymphoproliferation,...
X-linked lymphoproliferative disease (XLP1) is a rare primary immunodeficiency characterized by EBV-triggered immune dysregulation, lymphoproliferation, dysgammaglobulinemia, and lymphoma. Early childhood mortality from overwhelming inflammation is expected in most patients. The only curative therapy is hematopoietic stem cell transplant (HSCT); however, whether to perform HSCT on an asymptomatic patient remains debatable. This uncertainty arises because the natural history of XLP1 patients without transplantation is not clear. In this case report, we present the natural history of XLP1 in a 43-year-old male patient who did not receive HSCT. We also review the literature on untransplanted XLP1 patients who lived into mid-adulthood. Despite surviving childhood presentations that are typically fatal, we found that these rare patients remain susceptible to manifestations of XLP1 decades later.
PubMed: 32908732
DOI: 10.1155/2020/8841571