Equis ISSN 2398-2977

Immunology: combined immunodeficiency

Synonym(s): CID, Severe combined immunodeficiency disease, SCID

Contributor(s): Cody Coyne, Mark Holmes, Prof Derek Knottenbelt, Nicola Menzies-Gow, Vetstream Ltd

Introduction

  • Cause: inherited disorder preventing maturation of B- and T-lymphocyte cells in Arabian and Arabian crossbreeds. Inherited as an autosomal recessive trait. Results from a mutation on chromosome 9 encoding for the catalytic subunit of the enzyme DNA-dependent protein kinase (DNA-PK). This enzyme is essential for gene rearrangement that ultimately encodes the antigen-receptor complex on the cell surface of B- and T-lymphocytes. Absence of DNA-PK results in the elimination of lymphocyte precursors, and affected foals are born without functional B- and T-lymphocytes.
  • Signs: normal at birth but develop a variety of recurrent opportunistic infections within weeks to months   →   death by 5 months.
  • Diagnosis: 3 specific diagnostic tests.
  • Treatment: therapy for the opportunistic infection, bone marrow transplant.
  • Prognosis: always fatal without a transplant.
  • Prevention: do not use either parent of affected foals for breeding.

Pathogenesis

Etiology

  • Homozygosity of an autosomal recessive genetic trait.
  • Five base pair deletion in the gene encoding for the catalytic subunit of the enzyme DNA-dependent protein kinase (DNA-PK). This enzyme is essential for gene rearrangement that ultimately encodes the antigen-receptor complex on the cell surface of B- and T-lymphocytes. Absence of DNA-PK results in the elimination of lymphocyte precursors, and affected foals are born without functional B- and T-lymphocytes.

Predisposing factors

General
  • Breeding programs with heterozygotes perpetuate the problem by increasing the numbers of heterozygotes in population.

Specific

  • Arabian horse breed.
  • Both parents heterozygous for trait.
  • Age of onset of clinical signs determined by maternal immune levels and efficiency of colostral transfer of immunity to foal.

Pathophysiology

  • Breeding with heterozygous male and female   →    inherited autosomal recessive trait   →    deficiency of T-lymphocyte cells and lack B-lymphocytes with IgM molecules   →    not able to generate antigen-specific immune responses after infection or immunization.
  • Affected foals have normal complement systems, neutrophils and macrophages, produce secretory immunoglobulin components and still produce large granular lymphocytes suggestive of killer cells.
  • Foals appear normal at birth, grow normally and usually free of infections until loss of passively transferred immunity (6 weeks onwards). Foals may succumb to infections at an earlier point in time in cases of failure of passive transfer.
  • Normal catabolism of passively transferred maternal immunoglobulins   →    waning of passive humoral immunity   →    series of secondary infections (usually opportunistic micro-organisms), eg adenovirus   Equine adenovirus infection (EAI)  ,Pneumocystis carinii  Pneumocystis carinii  , Cryptosporidiumspp   Cryptosporidium spp  ,Rhodococcus equi    Rhodococcus equi  and various other bacteria.

Timecourse

  • Death usually by 5-6 months of age.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references fromPubMedandVetMedResource.
  • Tarr C J et al(2014)The carrier prevalnce of severe combined immunodeficiency, lavendar foal syndrome and cerebellar abiotrophy in Arabian horses in South Africa.Equine Vet J46(4), 512-514PubMed.
  • Christmas M V & Scarratt W K (2008)Immunodeficiency disorders in horses.Vet Clin North Am Equine Pract24(2), 299-310PubMed.
  • Piro Met al(2008)Frequency of the severe combined immunodeficiency disease gene among horses in Morocco.Equine Vet J40(6), 590-591PubMed.
  • Ding Qet al(2002)DNA-PKcs mutations in dogs and horses: allele frequency and association with neoplasia.Gene283(1), 263-269PubMed.
  • Shin E K, Perryman L E & Meed K (1997)Evaluation of a test for identification of Arabian horses heterozygous for the severe combined immunodeficiency trait.JAVMA211(10), 1268-1270PubMed.
  • Bue C Met al(1986)Correction of severe combined immunodeficiency by bone marrow transplantation.Transplantation42(1), 14-19PubMed.


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