Clinical, Immunological, and Molecular Characterization of Hyper-IgM Syndrome Due to CD40 Deficiency in Eleven Patients

Al‐Saud, Bandar; Alsum, Zobaida; Alassiri, Hanadi; Al-Ghonaium, Abdulaziz; Al‐Muhsen, Saleh; Al-Dhekri, Hasan; Arnaout, Rand; Alsmadi, Osama; Borrero, Esteban; Abu-staiteh, Asma’; Rawas, Faisal; Al‐Mousa, Hamoud; Hawwari, Abbas

doi:10.1007/s10875-013-9951-9

Cited by 52 publications

(24 citation statements)

References 25 publications

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“…Moreover, mutations concerning genes involved in Tfh cell differentiation and/or Tfh–B cell interaction (e.g. ICOS , SH2D1A , CD40‐CD40L ) result in primary immunodeficiency diseases and are associated with severe opportunistic infections , contrary to what was observed in TOL. Of course, the most convincing experiment such as an in vitro assay to measure the response of recipient Tfh cells against self‐restricted alloantigen using donor spleen lysates would have been better.…”

Section: Discussionmentioning

confidence: 97%

Renal Operational Tolerance Is Associated With a Defect of Blood Tfh Cells That Exhibit Impaired B Cell Help

Chenouard

Chesneau

Nguyen

et al. 2017

American Journal of Transplantation

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Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper (Tfh) cells play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh cells from TOL displayed a modified gene expression profile, failed to produce interleukin-21, and were unable to induce IgG production by naive B cells. This Tfh defect is linked to a low incidence of postgraft de novo donor-specific antibody (dnDSA) immunization, suggesting that the lack of Tfh cells in TOL may induce a protolerogenic environment with reduced risk of developing dnDSA. Finally, we showed that elevated Tfh in STA precedes the occurrence of dnDSA during an alloresponse. These data provide new insights into the mechanisms of antibody response in operational tolerance. Disrupted homeostasis and impaired Tfh function in TOL could lead to a reduced risk of developing dnDSA and suggest a predictive role of blood Tfh cells on the occurrence of dnDSA in transplant recipients.

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Section: Discussionmentioning

confidence: 97%

Renal Operational Tolerance Is Associated With a Defect of Blood Tfh Cells That Exhibit Impaired B Cell Help

Chenouard

Chesneau

Nguyen

et al. 2017

American Journal of Transplantation

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“…Since its description in 2001 (Ferrari et al 2001) only fourteen patients with CD40 deficiency from ten unrelated families have been reported to date, and with the exception of one patient of Italian descent, the rest are from Middle Eastern countries Mazzolari et al 2007;Al-Dhekri et al 2012;Al-Saud et al 2013). We report an additional adult patient of Iranian/ French Canadian decent with a novel mutation in CD40, presenting later in life and with a milder phenotype.…”

Section: Progressive Ataxia and Recurrent Pneumonia In A 20-month-oldmentioning

confidence: 83%

Abstracts from The Immunodeficiency Canada–CSACI symposium

2015

LymphoSign Journal

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“…B-cell deficient mice are susceptible to infection (63), as well as patients with hyper IgM syndrome due to either mutations in CD40 or CD40 ligand (64, 65). Consistent with these findings, both CD40−/− or CD40L−/− mice are also susceptible to Pneumocystis .…”

Section: Immunity Of Pneumocystis Infectionmentioning

confidence: 99%

Pathological and protective immunity to Pneumocystis infection

Eddens

Kolls

2014

Semin Immunopathol

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Pneumocystis jirovecii is a common opportunistic infection in the HIV-positive population and is re-emerging as a growing clinical concern in the HIV-negative immunosuppressed population. Newer targeted immunosuppressive therapies and the discovery of rare genetic mutations have furthered our understanding of the immunity required to clear Pneumocystis infection. The immune system can also mount a pathologic response against Pneumocystis following removal of immunosuppression and result in severe damage to the host lung. The current review will examine the most recent epidemiologic studies about the incidence of Pneumocystis in the HIV-positive and HIV-negative populations in the developing and developed world and will detail methods of diagnosis for Pneumocystis pneumonia. Finally, this review aims to summarize the known mediators of immunity to Pneumocystis and detail the pathologic immune response leading to Pneumocystis-related immune reconstitution inflammatory syndrome.

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Clinical, Immunological, and Molecular Characterization of Hyper-IgM Syndrome Due to CD40 Deficiency in Eleven Patients

Abstract: To our knowledge, this report provides the largest cohort of patients with this disease with a very long follow-up period. Our cohort showed variable disease severity

Cited by 52 publications

References 25 publications

Renal Operational Tolerance Is Associated With a Defect of Blood Tfh Cells That Exhibit Impaired B Cell Help

Renal Operational Tolerance Is Associated With a Defect of Blood Tfh Cells That Exhibit Impaired B Cell Help

Abstracts from The Immunodeficiency Canada–CSACI symposium

Pathological and protective immunity to Pneumocystis infection

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