Liver disease predicts mortality in patients with X-linked immunodeficiency with hyper-IgM but can be prevented by early hematopoietic stem cell transplantation

Azzu, Vian; Kennard, Lucinda; Morillo-Gutierrez, Beatriz; Slatter, Mary; Edgar, J. D. M.; Kumararatne, Dinakantha; Griffiths, William J.

doi:10.1016/j.jaci.2017.06.036

Cited by 16 publications

(13 citation statements)

References 24 publications

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“…Transjugular intrahepatic portosystemic shunts have used, but with unclear success . Liver transplantation has been performed, but the outcome has not been very encouraging overall with recurrent disease in the transplanted liver in some . Other liver conditions noted in some CVID patients are primary biliary cirrhosis and granulomatous disease.…”

Section: Clinical Spectrummentioning

confidence: 99%

Common variable immune deficiency: Dissection of the variable

Cunningham‐Rundles

2018

Immunological Reviews

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Summary Starting about 60 years ago, a number of reports appeared that outlined the severe clinical course of a few adult subjects with profound hypogammaglobinemia. Puzzled by the lack of family history and adult onset of symptoms in most, the name “acquired” hypogammaglobinemia was given, but later altered to the current name common variable immune deficiency (CVID). Pathology reports remarked on the loss of lymph node architecture and paucity of plasma cells in lymphoid tissues in these subjects. While characterized by reduced serum IgG and IgA and often IgM, and thus classified amongst the B cell defects, an increasing number of cellular defects in these patients have been recognized over time. In the early years, severe respiratory tract infections commonly led to a shortened life span, but the wide spread availability of immune globulin concentrates for the last 25 years has improved survival. However, chronic non-infectious inflammatory and autoimmune conditions have now emerged as challenging clinical problems; these require further immunologic understanding and additional therapeutic measures. Recent study of this phenotypic syndrome have provided an increasingly fertile ground for the identification of autosomal recessive and now more commonly, autosomal dominant gene defects which lead to the loss of B cell development in this syndrome.

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Section: Clinical Spectrummentioning

confidence: 99%

Common variable immune deficiency: Dissection of the variable

Cunningham‐Rundles

2018

Immunological Reviews

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“…Our patient did not have any clinical and laboratory signs of liver disease and also imaging studies including ultrasonography were all normal. On the other hand, in Azzu et al's study [ 5 ], crude mortality was higher in liver disease group (38%) compared with the group without liver disease (6%). Kaplan-Meier log-rank analysis showed decreased survival in XHIGM patients with liver disease [ 5 ].…”

Section: Discussionmentioning

confidence: 85%

“…Azzu V et al [ 5 ] found a higher prevalence of liver disease (33%) in XHIGM patients compared with most other studies, approximately 20% in data from a European registry and 6% in two US registries. In CVID patients, a recent study found liver disease in 5% of a cohort of 261 patients [ 12 ].…”

Section: Discussionmentioning

confidence: 93%

“…In a recent retrospective study in both transplanted or nontransplanted XHIGM patients, the median postdiagnosis survival was 25 years [ 1 ]. Azzu V et al [ 5 ] have reported that Ig replacement treated, CD40L deficient patients can live at least into the 4th decade without HSCT but that the burden of liver disease is as high as 40% in those who have not received HSCT.…”

Section: Introductionmentioning

confidence: 99%

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An X-Linked Hyper-IgM Patient Followed Successfully for 23 Years without Hematopoietic Stem Cell Transplantation

Kütükçüler

Karaca

Aksu

et al. 2018

Case Reports in Immunology

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When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patient regarding hematopoietic stem cell transplantation or intravenous immunoglobulin replacement therapy with P. jiroveci prophylaxis. A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media. His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping and inadequate specific antibody responses. He was diagnosed as common variable immunodeficiency and began to receive intravenous immunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremely well and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand his molecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found in CD40LG gene. The mother was heterozygous carrier for this mutation and his sister did not have any mutation. Flow cytometric analysis for CD40LG expression on activated T cells showed highly decreased, but not absent, CD40LG expression. In conclusion, diagnostic delay is a clinical problem for patients with CD40LG deficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemic patients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined for CD40LG expression on activated T lymphocytes. Secondly, type of CD40LG mutations leads to enormous interpatient variations regarding serum IgM levels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or without hematopoietic stem cell therapy.

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“…This approach currently includes immunoglobulin replacement (IgR), antimicrobial prophylaxis, close monitoring for complications, and careful precautions to avoid Cryptosporidium species exposure. Liver disease is the most significant predictor of mortality (67,69) and, together with severe infections, represents the major cause of death (64).…”

Section: The Example Of Cd40l Deficiency: Hsct Vs Long-term Supportimentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation for Combined Immunodeficiencies, on Behalf of IEWP-EBMT

Neven

Ferrua

2020

Front. Pediatr.

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Liver disease predicts mortality in patients with X-linked immunodeficiency with hyper-IgM but can be prevented by early hematopoietic stem cell transplantation

Cited by 16 publications

References 24 publications

Common variable immune deficiency: Dissection of the variable

Common variable immune deficiency: Dissection of the variable

An X-Linked Hyper-IgM Patient Followed Successfully for 23 Years without Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation for Combined Immunodeficiencies, on Behalf of IEWP-EBMT

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