Research

Diagnosis of primary antibody and complement immunodeficiencies in young adults after a first invasive bacterial infection.

Clin Microbiol Infect. 2017 Feb 10;:

Authors: Sanges S, Wallet F, Blondiaux N, Theis D, Verin I, Vachée A, Dessein R, Faure K, Viget N, Senneville E, Leroy O, Maury F, Just N, Poissy J, Mathieu D, Prévotat A, Chenivesse C, Scherpereel A, Smith G, Lopez B, Rosain J, Fremeaux-Bacchi V, Hachulla E, Hatron PY, Bahuaud M, Batteux F, Launay D, Labalette M, Lefèvre G

Abstract
OBJECTIVES: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults.
METHODS: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in 3 centers during a 3-year period. Eighteen to forty year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI) or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening.
RESULTS: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in 7 (19%): 2 cases of common variable immunodeficiency revealed by SP bacteremia, 1 case of idiopathic primary hypogammaglobulinemia and 2 cases of complement (C6 and C7) deficiency revealed by NM meningitis, 1 case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteremia, and 1 case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteremia, respectively.
CONCLUSION: PID screening should be considered after a first unexplained invasive encapsulated-bacteria infection in young adults.

PMID: 28192236 [PubMed – as supplied by publisher]

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Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study.

Clin Microbiol Infect. 2017 Feb 10;:

Authors: Parize P, Muth E, Richaud C, Gratigny M, Pilmis B, Lamamy A, Mainardi JL, Cheval J, de Visser L, Jagorel F, Ben Yahia L, Bamba G, Dubois M, Join-Lambert O, Leruez-Ville M, Nassif X, Lefort A, Lanternier F, Suarez F, Lortholary O, Lecuit M, Eloit M

Abstract
OBJECTIVE: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance.
METHODS: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically-relevant viruses and bacteria at inclusion.
RESULTS: Clinically-relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (Kappa test=0.2 [95% confidence interval, 0.03 to 0.48]). However, clinically-relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, P<0.001), and even when the latter were continued over 30 days (19/101 (19%), P=0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, confidence interval 95%: 0.95-1).).
CONCLUSIONS: Untargeted next-generation sequencing has a high negative predictive value and detects more clinically-relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults.

PMID: 28192237 [PubMed – as supplied by publisher]

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Autoimmune and inflammatory manifestations occur frequently in primary immunodeficiencies.

J Allergy Clin Immunol. 2017 Feb 09;:

Authors: Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N, members of the CEREDIH French PID study group

Abstract
BACKGROUND: Primary immunodeficiencies (PIDs) are inherited diseases associated with a considerably increase in susceptibility to infections. It is known that PIDs can also predispose to cancer and immune diseases including allergy, autoimmunity and inflammation.
OBJECTIVE: We aimed at determining the incidence of autoimmunity and inflammation in PID patients.
METHODS: We have retrospectively screen 2183 consecutive cases of PID in the French CEREDIH registry for the occurrence of autoimmunity and inflammation.
RESULTS: One or more autoimmune and inflammatory complications were noted in 26.2% of patients, with a risk of onset throughout the patient’s lifetime. The risk of autoimmune cytopenia was at least 120 times higher than in the general population, the risk of inflammatory bowel disease in children 80 times higher and the risk of other autoimmune manifestations was approximately 10 times higher. Remarkably, all types of PID were associated with a risk of autoimmune and inflammatory complications, although the greatest risk was associated with T cell PIDs and common variable immunodeficiency. The occurrence of autoimmune disease is a negative prognostic factor for survival.
CONCLUSIONS: Our results provide the basis for a detailed, prospective evaluation of autoimmunity and inflammation in the context of PID, with a view to accurately assessing these risks and describing the possible impact of medical intervention.

PMID: 28192146 [PubMed – as supplied by publisher]

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[Immunological alterations in common variable immunodeficiency].

Rev Alerg Mex. 2017 Jan-Mar;64(4):87-108

Authors: Berrón-Ruiz L

Abstract
Common variable immunodeficiency (CVID) is the largest group of symptomatic primary immune deficiencies; it is characterized by hypogammaglobulinemia, poor response to vaccines and increased susceptibility to infections. Cellular phenotypes and abnormalities have been described both in adaptive and innate immune response. Several classifications of common variable immunodeficiency are based on defects found on T and B cells, which have been correlated with clinical manifestations. In recent years, significant progress has been made in elucidating the genetic mechanisms that result in a IDCV phenotype. Massive sequencing technologies have favored the description of mutations in several genes, but only in 2 % to 10 % of patients. These monogenetic defects are: ICOS, TNFRSF13B (TACI), TNFRS13C (BAFFR), TNRFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), (CD27), LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R, VAV1, RAC1, BLK, IKZF1 (IKAROS) and IRF2BP2. These findings have provided a possible explanation for the pathogenesis of IDCV, since these molecules play an important role in the co-operation between B and T cells in the germinal center, as well as in intrinsic signaling pathways of both.

PMID: 28188716 [PubMed – in process]

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[Hematopoietic stem cells transplant in patients with common variable immunodeficiency. Is a therapeutic option?]

Rev Alerg Mex. 2017 Jan-Mar;64(1):121-125

Authors: Cambray-Gutiérrez JC, Herrera-Sánchez DA, López-Pérez P, Chávez-García A, Yamazaki-Nakashimada MA

Abstract
BACKGROUND: Patients with common variable immunodeficiency show higher incidence of sinopulmonary and gastrointestinal infections, as well as lymphoproliferative and autoimmune diseases. The treatment of choice is replacement therapy with human gamma-globulin. Hematopoietic stem cell transplantation is a non-conventional therapeutic modality.
CASE REPORT: Twenty-six-year old woman with no family or hereditary history of primary immune deficiencies or consanguinity, with repeated episodes of otitis, sinusitis, gastroenteritis and bronchitis since childhood. At adolescence, she was diagnosed with common variable immunodeficiency; she was prescribed intravenous gamma-globulin, broad-spectrum antimicrobials and macrolides. At 22 years of age, she underwent hematopoietic stem cell transplantation owing to continued severe infections. At 4 months, post-transplantation she was diagnosed with hypothyroidism and ovarian insufficiency. During the following 3 years, she had no infections, but at 25 years of age she had immune thrombocytopenic purpura diagnosed, which persists together with Raynaud’s disease and upper respiratory tract persistent infections. At the moment of this report she is being treated with intravenous gamma-globulin and receiving prophylaxis with clarithromycin, without steroids or danazol.
CONCLUSIONS: Given the high rate of morbidity and mortality associated and immune reconstitution failure, hematopoietic stem cell transplantation should be carefully evaluated in patients with treatment-unresponsive infections or lymphoproliferative disorders.

PMID: 28188718 [PubMed – in process]

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[Clinical symptoms in IgA deficiency].

Rev Alerg Mex. 2017 Jan-Mar;64(1):34-39

Authors: De Oliveira-Serra FA, Mosca T, Santos de Menezes MD, Carvalho-Neves Forte W

Abstract
BACKGROUND: IgA deficiency is the most common primary immunodeficiency. Early diagnosis and clinical follow-up may improve the quality of life of patients with IgA deficiency. To this end, IgA deficiency should be further studied and better understood on its clinical manifestations.
OBJECTIVE: To determine IgA deficiency clinical manifestations.
METHODS: Cross-sectional, retrospective, exploratory study, where the medical records of 39 patients with IgA deficiency were analyzed.
RESULTS: Among the analyzed cases, 10 patients were diagnosed with total IgA deficiency and 29 patients with partial IgA deficiency. Partial and total IgA deficiency main clinical manifestations were allergic rhinoconjunctivitis and allergic asthma. In total IgA deficiency, in addition to allergic diseases, a statistically significant number (p < 0.05) of cases of infection-related rhinosinusitis, tonsillitis and conjunctivitis were also observed.
CONCLUSION: This study showed that the main clinical manifestations in IgA deficiency were allergic rhinoconjunctivitis and allergic asthma. In addition, patients with total IgA deficiency showed a significant increase in infection-related rhinosinusitis, tonsillitis and conjunctivitis, when compared with patients with partial IgA deficiency.

PMID: 28188711 [PubMed – in process]

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Risk Factors in Children Older than 5 Years with Pneumococcal Meningitis: Data from a National Network.

Pediatr Infect Dis J. 2016 Dec 13;:

Authors: Hénaff F, Levy C, Cohen R, Picard C, Varon E, Le Guen CG, Launay E, French Group of Pediatric Infectious Diseases (GPIP)

Abstract
INTRODUCTION: The occurrence of meningitis in children > 5 years old may be associated with specific predisposing factors that can be anatomic, such as cerebrospinal fluid (CSF) fistula or breach, or related to genetic susceptibility or N inborn or acquired immunologic defect. This study aimed to assess the anatomical and immunologic risk factors in children > 5 years old with pneumococcal meningitis and prospectively enrolled in the French national meningitis network.
METHODS: We analyzed all data for children 5 to 15 years old with a diagnosis of pneumococcal meningitis between 2001 and 2013. We describe the frequency and typology of the anatomic or immunologic risk factors, the clinical features and the pneumococcal serotypes.
MAIN RESULTS: Among the 316 patients with pneumococcal meningitis, the mortality rate was 9.5%, and 23.1% of cases presented complications (abscess, coma, hemodynamic failure, thrombophlebitis cerebral or deafness). In total, 108 children (34%) showed risk factors, the most frequent being anatomic: 70 cases (22.8%) were related to a CSF breach or fistula and 55 (17.9%) to immunodeficiency, primary or acquired. Serotype data were available for 207 pneumococcal isolates (65.5%). The most frequent serotypes were 3, 18C, 19A, and 19F between 2001 and 2009 and 19F, 3, 19A, 12F, 22F, 17F and 24F after 2009.
DISCUSSION: We describe the largest cohort of children > 5 years old with pneumococcal meningitis. One third of the children had risk factors justifying a complete immunologic and radiologic work-up.

PMID: 28187060 [PubMed – as supplied by publisher]

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