Difference between revisions of "Immunodeficiency syndrome"

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The most reported immunodeficiency is specific immunoglobulin deficiency, particularly IgA, thought to be due to not an absolute lack of IgA but specific concentration in target organs such as mucosal surfaces, such as is seen in [[German Shepherd]] dog with [[anal furunculosis]] (IgA deficiency)<ref>Peters IR ''et al'' (2003) Quantitative real-time RT-PCR measurement of mRNA encoding-chain, pIgR and J-chain from canine duodenal mucosa. ''J Immunol Methods'' '''275''':213-222</ref> and [[lethal acrodermatitis]] in [[English bull Terrier]]s (IgA deficiency)<ref>McEwan NA ''et al'' (2003) Immunoglobulin levels in bull terriers suffering from lethal acrodermatitis. ''Vet Immunol Immunopathol'' '''96''':235-238</ref>, where there is sufficient circulating IgA, but insufficient excretion at the epidermal surface.  
 
The most reported immunodeficiency is specific immunoglobulin deficiency, particularly IgA, thought to be due to not an absolute lack of IgA but specific concentration in target organs such as mucosal surfaces, such as is seen in [[German Shepherd]] dog with [[anal furunculosis]] (IgA deficiency)<ref>Peters IR ''et al'' (2003) Quantitative real-time RT-PCR measurement of mRNA encoding-chain, pIgR and J-chain from canine duodenal mucosa. ''J Immunol Methods'' '''275''':213-222</ref> and [[lethal acrodermatitis]] in [[English bull Terrier]]s (IgA deficiency)<ref>McEwan NA ''et al'' (2003) Immunoglobulin levels in bull terriers suffering from lethal acrodermatitis. ''Vet Immunol Immunopathol'' '''96''':235-238</ref>, where there is sufficient circulating IgA, but insufficient excretion at the epidermal surface.  
  
IgA deficiency has also been reported in the [[Shar Pei]], [[Beagle], [[English Cocker Spaniel]], [[Irish Wolfhound]] (recurrent rhinitis, [[pneumonia]])<ref>Clercx C ''et al'' (2003) Rhinitis/bronchopneumonia syndrome in Irish Wolfhounds. ''J Vet Intern Med'' '''17''':843-849</ref><ref>Leisewitz AL ''et al'' (1997) Suspected primary immunodeficiency syndrome in three related Irish wolfhounds. ''J Small Anim Pract'' '''38(5)''':209-212</ref>, [[Rottweiler]], [[Weimaraner]] ([[hypertrophic dystrophy]]-associated IgG deficiency)<ref>Day MJ ''et al'' (1997) Low serum immunoglobulin concentrations in related Weimaraner dogs. ''J Small Anim Pract'' '''38''':311-315</ref><ref>Abeles V ''et al'' (1999) Hypertrophic osteodystrophy in six Weimaraner puppies associated with systemic signs. ''Vet Rec'' '''145''':130-134</ref>, [[Cavalier King Charles Spaniel]] (IgG deficiency), [[English Bull Terrier]], [[American Foxhound]], [[Cocker Spaniel]], [[Boston Terrier]], [[Basenji]] and [[Miniature Dachshund]] (IgG deficiency related [[pneumonia]])<ref>Day MJ (1999) Immunodeficiency disease. In: Clinical Immunology of the Dog and Cat. MJ Day. Manson publishing, London. pp:197-215</ref>.
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IgA deficiency has also been reported in the [[Shar Pei]], [[Beagle], [[English Cocker Spaniel]], [[Irish Wolfhound]] (recurrent rhinitis, [[pneumonia]])<ref>Clercx C ''et al'' (2003) Rhinitis/bronchopneumonia syndrome in Irish Wolfhounds. ''J Vet Intern Med'' '''17''':843-849</ref><ref>Leisewitz AL ''et al'' (1997) Suspected primary immunodeficiency syndrome in three related Irish wolfhounds. ''J Small Anim Pract'' '''38(5)''':209-212</ref>, [[Rottweiler]], [[Weimaraner]] ([[hypertrophic osteodystrophy]]-associated IgG deficiency)<ref>Day MJ ''et al'' (1997) Low serum immunoglobulin concentrations in related Weimaraner dogs. ''J Small Anim Pract'' '''38''':311-315</ref><ref>Abeles V ''et al'' (1999) Hypertrophic osteodystrophy in six Weimaraner puppies associated with systemic signs. ''Vet Rec'' '''145''':130-134</ref>, [[Cavalier King Charles Spaniel]] (IgG deficiency), [[English Bull Terrier]], [[American Foxhound]], [[Cocker Spaniel]], [[Boston Terrier]], [[Basenji]] and [[Miniature Dachshund]] (IgG deficiency related [[pneumonia]])<ref>Day MJ (1999) Immunodeficiency disease. In: Clinical Immunology of the Dog and Cat. MJ Day. Manson publishing, London. pp:197-215</ref>.
  
 
Secondary causes of immunodeficiency include:
 
Secondary causes of immunodeficiency include:

Revision as of 20:17, 17 February 2013

Primary hereditary immunodeficiency disorders are uncommon in the dog and associated with a range of infectious, inflammatory, allergic and autoimmune diseases.

The most reported immunodeficiency is specific immunoglobulin deficiency, particularly IgA, thought to be due to not an absolute lack of IgA but specific concentration in target organs such as mucosal surfaces, such as is seen in German Shepherd dog with anal furunculosis (IgA deficiency)[1] and lethal acrodermatitis in English bull Terriers (IgA deficiency)[2], where there is sufficient circulating IgA, but insufficient excretion at the epidermal surface.

IgA deficiency has also been reported in the Shar Pei, [[Beagle], English Cocker Spaniel, Irish Wolfhound (recurrent rhinitis, pneumonia)[3][4], Rottweiler, Weimaraner (hypertrophic osteodystrophy-associated IgG deficiency)[5][6], Cavalier King Charles Spaniel (IgG deficiency), English Bull Terrier, American Foxhound, Cocker Spaniel, Boston Terrier, Basenji and Miniature Dachshund (IgG deficiency related pneumonia)[7].

Secondary causes of immunodeficiency include:

The best-defined canine lymphoid immunodeficiency is X-linked severe combined immunodeficiency (X-SCID) described in the basset hound and corgi15. Affected dogs have been studied in research colonies as a model for the equivalent disease in humans. Canine X-SCID involves a mutation in the common chain of receptor molecules for the cytokines IL-2, IL-4, IL-7, IL-15 and IL-19. More recently, a non-X-linked form of SCID has been described in a colony of Jack Russell terriers16. The genetic defect in these dogs relates to defective DNA-dependent protein kinase that is responsible for molecular recombination giving rise to functional T and B lymphocyte receptors. This form of SCID is similar to that that has long been recognised in Arabian horses. Mexican hairless dogs have been described as having subnormal immunoglobulin concentration, impaired delayed hypersensitivity response and depletion of lymphoid tissue. The association of hairlessness and immunodeficiency is well recognised in inbred laboratory strains of 'nude' athymic rats and mice.

THERAPEUTIC APPROACHES TO IMMUNODEFICIENCY

Therapeutic options for animals with primary immunodeficiency disease are limited. Most cases are fatal, but symptomatic and antimicrobial therapy can sometimes prolong life for restricted periods. Crude immunomodulatory drugs are sometimes administered, but the effects of these are poorly documented. A range of experimental therapies have been attempted in dogs with cyclic haematopoiesis, particularly recombinant cytokine therapy (e.g., canine granulocyte colony stimulating factor and stem cell factor), and bone marrow transplantation. Bone marrow transplantation has also been successfully used to experimentally treat dogs with X-SCID and CLAD17. Such canine studies are generally performed from the perspective of using the dog as a model for developing therapy for the counterpart human diseases. The availability of these canine models will in future permit the testing of gene replacement therapy for immunodeficiency. A preliminary study has shown that administration of the canine G-CSF gene in a lentivirus vector resulted in elevation of blood neutrophils in a grey collie with cyclic neutropenia for over 17 months18.

Of more relevance and importance is the elimination of such traits from breeding stock, by not breeding from affected animals and by genetic screening of breeding pairs where molecular testing exists. This approach has been very successful for the CLAD mutation in Irish setters, where widespread testing and the collaboration of the breed society have meant that the goal of eliminating this trait from the breed is becoming achievable19.

References

1. .

2. German AJ, Hall EJ and Day MJ. Relative deficiency in IgA production by duodenal explants from German shepherd dogs with small intestinal disease. Vet Immunol Immunopathol 2000; 76: 25-43.

3. .

4. .

5. Leisewitz AL, Spencer JA, Jacobson LS, Schroeder H. Suspected primary immunodeficiency syndrome in three related Irish wolfhounds. J Small Anim Pract 1997; 38: 209-212.

6. .

7. .

9. Foale RD, Herrtage ME and Day MJ. Retrospective study of 25 young Weimaraners with low serum immunoglobulin concentrations and inflammatory disease. Vet Rec 2003; 153: 553-558.

10. .

11. Lobetti RG. Pneumocystis carinii infection in miniature dachshunds. Comp Cont Educ Pract Vet 2001; 23: 320-324.

12. Day MJ. Possible immunodeficiency in related Rottweiler dogs. J Small Anim Pract 1999; 40: 561-568.

13. Lanevschi A, Daminet S, Niemeyer GP, Lothrop CD. Granulocyte colony-stimulating factor deficiency in a Rottweiler with chronic idiopathic neutropenia. J Vet Intern Med 1999; 13: 72-75.

14. Trowald-Wigh G, Ekman S, Hansson K, et al. Clinical, radiological and pathological features of 12 Irish setters with canine leucocyte adhesion deficiency. J Small Anim Pract 2000; 41: 211-217.

15. Felsburg PJ, Hartnett BJ, Henthorn PS, et al. Canine X-linked severe combined immunodeficiency. Vet Immunol Immunopathol 1999; 69: 127-135.

16. Meek K, Kienker L, Dallas C et al. SCID in Jack Russell terriers: a new animal model of DNA-PKcs deficiency. J Immunol 2001; 167: 2142-2150.

17. Creevy KE, Bauer TR, Tuschong LM et al. Mixed chimeric hematopoietic stem cell transplant reverses the disease phenotype in canine leukocyte adhesion deficiency. Vet Immunol Immunopathol 2003; 95: 113-121.

18. Yanay O, Barry SC, Katen LJ et al. Treatment of canine cyclic neutropenia by lentivirus-mediated G-CSF delivery. Blood 2003; 102: 2046-2052.

19. Jobling AJ, Ryan J and Augusteyn RC. The frequency of the canine leukocyte adhesion deficiency (CLAD) allele within the Irish setter population of Australia. Aust Vet J 2003; 81: 763-765. Speaker Information (click the speaker's name to view other papers and abstracts submitted by this speaker)

Michael J. Day, BSc, BVMS(Hons), PhD, FASM, DECVP, MRC Path, FRCVS School of Clinical Veterinary Science, University of Bristol UK Speaker Information: Michael Day qualified from Murdoch University (Western Australia) in 1982. After a period in small animal practice he returned to Murdoch to complete a Residency in Microbiology and Immunology, and a PhD involving collaborative research with the Royal Perth Hospital. Michael held postdoctoral positions in experimental immunology at the Universities of Bristol and Oxford, and in 1990 returned to Bristol where he is currently Professor of Veterinary Pathology and Director of Laboratory Diagnostic Services. His research interests cover experimental models of autoimmunity and a range of companion animal immune-mediated and infectious diseases. Michael has published widely in the field of immunopathology, is author of the textbook Clinical Immunology of the Dog and Cat and has co-edited the BSAVA Manual of Canine and Feline Haematology and Transfusion Medicine and the upcoming text Arthropod-Borne Infectious Diseases of the Dog and Cat. He is a member of the editorial boards of the Journal of Comparative Pathology and Veterinary Dermatology. He has been the recipient of the BSAVA Amoroso Award for outstanding contribution to small animal studies (1999), the BSAVA Petsavers Award (2000) and the RCVS Trust's G. Norman Hall Medal for outstanding research into animal diseases (2003).

References

  1. Peters IR et al (2003) Quantitative real-time RT-PCR measurement of mRNA encoding-chain, pIgR and J-chain from canine duodenal mucosa. J Immunol Methods 275:213-222
  2. McEwan NA et al (2003) Immunoglobulin levels in bull terriers suffering from lethal acrodermatitis. Vet Immunol Immunopathol 96:235-238
  3. Clercx C et al (2003) Rhinitis/bronchopneumonia syndrome in Irish Wolfhounds. J Vet Intern Med 17:843-849
  4. Leisewitz AL et al (1997) Suspected primary immunodeficiency syndrome in three related Irish wolfhounds. J Small Anim Pract 38(5):209-212
  5. Day MJ et al (1997) Low serum immunoglobulin concentrations in related Weimaraner dogs. J Small Anim Pract 38:311-315
  6. Abeles V et al (1999) Hypertrophic osteodystrophy in six Weimaraner puppies associated with systemic signs. Vet Rec 145:130-134
  7. Day MJ (1999) Immunodeficiency disease. In: Clinical Immunology of the Dog and Cat. MJ Day. Manson publishing, London. pp:197-215