scholarly journals TACI Mutations in Primary Antibody Deficiencies: A Nationwide Study in Greece

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 827
Author(s):  
Ioannis Kakkas ◽  
Gerasimina Tsinti ◽  
Fani Kalala ◽  
Evangelia Farmaki ◽  
Alexandra Kourakli ◽  
...  
Keyword(s):  
Primary Antibody ◽  
Compound Heterozygous ◽  
Igg Subclass Deficiency ◽  
Primary Antibody Deficiencies ◽  
Lymph Node Enlargement ◽  
History Of ◽  
Polymerase Chain ◽  
Clinically Significant ◽  
Autoimmune Cytopenias ◽  
Common Variable

Background and objectives: Monoallelic (heterozygous) or biallelic (homozygous or compound heterozygous) TACI mutations have been reported as the most common genetic defects in patients with common variable immunodeficiency (CVID), which is the most common clinically significant primary immunodeficiency in humans. The aim of our study was to evaluate the prevalence and any correlations of TACI defects in Greek patients with primary antibody deficiencies. Materials and Methods: 117 patients (male/female: 53/64) with CVID (110) and a combined IgA and IgG subclass deficiency (7) with a CVID-like clinical phenotype were enrolled in the study. Genomic DNA was extracted from peripheral blood and the molecular analysis of the TACI gene was performed by PCR (Polymerase Chain Reaction) and sequencing of all 5 exons, including exon–intron boundaries. Results: Seventeen patients (14.5%) displayed TACI defects, four (23.5%) carried combined heterozygous mutations and 13 (76.5%) carried single heterozygous mutations. The most frequently detected mutation was C104R (58.8%), followed by I87N (23.5%) and A181E (11.8%), while R20C, C62Y, P151L, K188M and E236X mutations were present in only one patient each. Patients with TACI defects were more frequently male (p = 0.011) and displayed a benign lymphoproliferation (splenomegaly and lymph node enlargement, p = 0.047 and p = 0.002, respectively), had a history of tonsillectomy (p = 0.015) and adenoidectomy (p = 0.031) and more frequently exhibited autoimmune cytopenias (p = 0.046). Conclusions: Considering that accumulating evidence suggests several CVID patients have a complex rather than a monogenic inheritance, our data further support the notion that TACI mutations, particularly as monoallelic defects, should be primarily considered as susceptibility co-factors and/or modifiers of primary antibody deficiencies.

Influence Of RHCE Variant Genotypes On Anti-e Alloimmunization Risk In SCD Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2392-2392 ◽  
Author(s):  
Ross M Fasano ◽  
Mitchell G Bryski ◽  
Philippe Pary ◽  
Mohamadou Sene ◽  
Naomi L.C. Luban
Keyword(s):  
Statistical Significance ◽  
Compound Heterozygous ◽  
Exact Test ◽  
African Patient ◽  
Increased Risk ◽  
African Immigration ◽  
Two Generations ◽  
History Of ◽  
Clinically Significant ◽  
African Patients

Abstract Background A higher incidence of Red Blood Cell (RBC) alloimmunization exists in Sickle Cell Disease (SCD) than in any other multiply transfused population. The majority of the RBC alloantibodies are to Rh (D, C, c, E, e) and K antigens. Transfusing Rh and Kell matched RBCs substantially decreases alloimmunization rates in SCD patients; however clinically significant Rh antibodies with apparent common specificities persist as a result of altered RH alleles in SCD patients. Methods SCD patients with a history of ≥15 transfusions or having RBC alloantibody(ies) were consented and asked to complete an ethnicity survey defining patients as “African” (patient or both parents African-born), African American (parents and patient US-born), or other. RH genotyping was performed on all patients using RH Variant Beadchips (BioArray, Warren NJ). Medical records of patients were retrospectively reviewed and compared to RH genotype and ethnicity to determine the clinical impact of RH variants on alloimmunization. Fisher’s Exact test was used to determine statistical significance of correlations. Results Among 117 SCD patients genotyped, 67 (57.3%) had alloantibodies, with a median of 50 transfusion exposures. RHCE variant haplotype frequencies for (C)ces, ces, ceAR, ceMO and ces(340) were 6.8%, 20.1%, 0.9%, 1.3% and 0.4%, respectively. Twenty-two patients were either homozygous (7), compound-heterozygous (5), or heterozygous for these RHCE variant haplotypes with a conventional RH E allele in-trans (10). Of these, approximately 32% (7/22) formed an anti-e alloantibodies after a median of 6 Rhe+ RBC transfusion exposures compared to 7.3% (7/95) of all other patients (p=0.0048). No anti-e alloantibodies were detected in 15/22 patients within the RHCE variant subgroup after 1436 Rhe+ RBC transfusions (median 66 transfusions/patient), yielding an anti-e alloantibody frequency of 0.45/100 units. Fifty percent (11/22) of patient in the RHCE variant subgroup formed an autoantibody, compared with 24% (19/78) of all other patients (p=0.0345). Approximately 32% (8/25) of the “African” patients were homozygous or compound heterozygous for a variant, as opposed to 10.7% of “Non-African” patients (p=0.0312); only 12.5% (1/8) of African patients with RHCE variant subgroup formed anti-e alloantibodies versus 46% of “Non-African” patients this subgroup (p= NS). Conclusion SCD patients with RHCE variant haplotypes are at increased risk for the formation of clinically significant anti-e alloantibodies, which may be inaccurately identified as autoantibodies in the absence of RH genotyping. This implies that RH genotyping should be either incorporated into the standard RBC phenotype evaluation in all SCD patients, or at least into the evaluation of any SCD patient with an autoantibody that demonstrates “e” specificity. We report similar RHCE variant allele frequencies compared to previously published SCD population studies; however we found a higher prevalence of homozygous and compound heterozygous RHCE variant genotypes in SCD patients less then two generations removed from African immigration. Confounding factors for anti-e alloimmunization risk in SCD patients with RHCE variant genotypes other than antigen disparity exist which may explain why “African” patients within the RHCE variant subgroup demonstrated lower anti-e alloimmunization compared to other patients in this group. Further study is warranted to further characterize the immunogenic potential of high incidence Rh antigens in individuals with RH variants, and the immunogenetic variables that affect alloimmunization overall. Disclosures: Fasano: ApoPharma: Honoraria.

Recurrent Pneumonias and Bronchiectasis - Is it an Immunodeficiency Disorder? - A Case Report

2020 ◽  
Vol 40 (2) ◽  
pp. 139-142
Author(s):  
Sumit Agrawal ◽  
S Shreeram ◽  
A Jha ◽  
B Prajapati
Keyword(s):  
Case Report ◽  
Past History ◽  
Pulmonary Infections ◽  
Primary Immunodeficiency Disorder ◽  
Recurrent Pneumonia ◽  
Immunodeficiency Disorder ◽  
History Of ◽  
Autoimmune Cytopenias ◽  
Common Variable ◽  
Low Serum

Common Variable Immunodeficiency (CVID) is a form of primary immunodeficiency disorder characterised by hypogammaglobulinemia and recurrent sino-pulmonary infections. Its diagnosis is based on the presence of low serum IgG (< 2 SD below normal for age) with or without low IgA/ IgM levels and presentation beyond two years of age. These children also have disorders of autoimmunity with majority of them presenting as autoimmune cytopenias, predominantly thrombocytopenia and some having anaemia and neutropenias. Here we report a nine years old boy with past history of recurrent pneumonia, presenting this episode with fungal pneumonia, thrombocytopenia and anaemia eventually diagnosed as CVID.

Novel mutations in the Dubin–Johnson syndrome gene ABCC2/MRP2 and associated biochemical changes

2012 ◽  
Vol 49 (6) ◽  
pp. 609-612 ◽  
Author(s):  
Manjit S Devgun ◽  
Adil M El-Nujumi ◽  
Geraldine J O'Dowd ◽  
Véronique Barbu ◽  
Raoul Poupon
Keyword(s):  
Polymerase Chain Reaction Amplification ◽  
Biochemical Changes ◽  
Compound Heterozygous ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Johnson Syndrome ◽  
Heterozygous Variant ◽  
History Of ◽  
Reaction Amplification ◽  
Polymerase Chain

A patient with sepsis and jaundice was admitted for diagnosis and treatment. Associated biochemical changes included increased C-reactive protein, conjugated bilirubin and gamma-glutamyltransferase, the duration of which was protracted. High urine coproporphyrin isomer-1 and immunostaining of liver tissue suggested Dubin–Johnson syndrome. DNA sequencing using polymerase chain reaction amplification of the ABCC2 gene revealed the patient to have a compound heterozygous variant of MRP2, a molecule involved in canalicular transport of bilirubin. There was a history of jaundice since infancy.

scholarly journals A Novel Point-of-Care Rapid Diagnostic Test for Screening Individuals for Antibody Deficiencies

2021 ◽  
Author(s):  
Shirli Israeli ◽  
Allison Golden ◽  
Melissa Atalig ◽  
Najla Mekki ◽  
Afef Rais ◽  
...  
Keyword(s):  
Diagnostic Test ◽  
Rapid Diagnostic Test ◽  
Common Variable Immunodeficiency ◽  
Point Of Care ◽  
Primary Antibody ◽  
Healthy Controls ◽  
Primary Antibody Deficiencies ◽  
Wide Range ◽  
Hyper Igm ◽  
Common Variable

Abstract Purpose No rapid diagnostic test exists to screen individuals for primary antibody deficiencies (PAD) at or near the point of care. In settings at risk for polio where live oral polio vaccine is utilized, undiagnosed PAD patients and cases with delayed diagnosis constitute a potential reservoir for neurovirulent polioviruses, undermining polio eradication. This research aimed to develop a rapid screening test suited for use in resource-limited settings to identify individuals with low immunoglobulin G (IgG) levels, enabling early diagnosis and appropriate treatment. Methods Three prototype tests distinguishing low and normal IgG levels were evaluated with a blinded panel of serum/plasma specimens from 32 healthy controls and 86 primary immunodeficiency-confirmed patients with agammaglobulinemia, common variable immunodeficiency, and hyper-IgM syndrome, including 57 not receiving IgG therapy. Prototype tests were compared to laboratory reference and clinical case definition. Results The leading prototype correctly identified 32 of 32 healthy controls. Among primary antibody deficiency patients not receiving IgG treatment, 17 of 19 agammaglobulinemia, 7 of 24 common variable immunodeficiency, and 5 of 14 hyper-IgM were correctly identified by the prototype, with 67% agreement with the reference assay. Conclusion The Rapid IgG Screen (RIgGS) test can differentiate between low IgG levels associated with agammaglobulinemia and normal IgG antibody levels. Differentiating CVID and hyper IgM was challenging due to the wide range in IgG levels and influence of high IgM. This test can facilitate the identification of patients with primary antibody deficiencies and support polio surveillance initiatives.

An unusual presentation of epigastric pain due to thrombophlebitis of a recanalised umbilical vein – case report

2019 ◽  
Vol 98 (8) ◽  
pp. 326-327 ◽  
Keyword(s):  
Liver Cirrhosis ◽  
Abdominal Pain ◽  
Case Report ◽  
Portal Hypertension ◽  
Liver Disease ◽  
Epigastric Pain ◽  
Umbilical Vein ◽  
History Of ◽  
Clinically Significant ◽  
Inflammatory Changes

Introduction: The umbilical vein can become recanalised due to portal hypertension in patients with liver cirrhosis but the condition is rarely clinically significant. Although bleeding from this enlarged vein is a known complication, the finding of thrombophlebitis has not been previously described. Case report: We report the case of a 62-year-old male with a history of liver cirrhosis due to alcoholic liver disease presenting to hospital with epigastric pain. A CT scan of the patient’s abdomen revealed a thrombus with surrounding inflammatory changes in a recanalised umbilical vein. The patient was managed conservatively and was discharged home the following day. Conclusion: Thrombophlebitis of a recanalised umbilical vein is a rare cause of abdominal pain in patients with liver cirrhosis.

Sign in / Sign up

Export Citation Format

Share Document