Luke Droney IMMUNOGLOBULIN LEVELS AND FUNCTION
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1 IMMUNOGLOBULIN LEVELS AND FUNCTION Interpret changes in immunoglobulin levels within the clinical context including - Immunodeficiency - Disorders characterised by hypergammaglobulinaemia, rheumatoid arthritis, chronic infection, inflammation, autoinflammation DDx for hypogamma (From Bonilla et al J ALLERGY CLIN IMMUNOL PRACT VOLUME 4, NUMBER 1, Jan/Feb 2016 good review of CVID)
2 Immunoglobulins and Immunodeficiency Immunodeficiency IgG IgA IgM IgE Comments CVID ê >2SD below mean Hyper- IgM syndrome ê ê or N ê ê - Low IgG plus one of IgA/M. Some say low IgA/M not required for diagnosis é or N - Low IgG with high or normal IgM XLP ê ê ê - Usually normal immunoglobulins prior to EBV infection AD- HIES N N N é é Usually serum IgE >2000. Impaired vaccine response AR- HIES (DOCK8) N N ê é é Decreased IgM in DOCK8 may differentiate from AD- HIES. Viral skin infections, atopy, eosinophilia. Typical SCID Leaky SCID/Omenn syndrome ê See comments ê ê - Extremely low levels of IgM and IgA. Maternal levels of IgG at birth, low by age 3 months ê ê ê é Very low IgG/A/M but usually increased IgE ADA/PNP deficiency - Variable depending on severity. Can be similar to Omenn syndrome. Severe phenotypes as for typical SCID. Adult onset may have normal immunoglobulins
3 HLA Class I deficiency (usually TAP deficiency) HLA Class II deficiency (usually CIITA deficiency) X- linked agamma/ar agamma é é é - Deficiency of IgG2/IgG4 reported ê ê ê - IgM increased in some cases ê ê ê ê IgM and IgA usually undetectable. May have small amounts of IgG, or even normal IgG in rare cases Wiskott- Aldrich syndrome N é N é Variable vaccine response. Depressed response to polysaccharide vaccines. Impaired T- B interactions, class switching/somatic hypermutation ALPS é é é - Polyclonal hypergamma IPEX (FoxP3 def) N é N é DiGeorge syndrome ê ê ê - May have increased B cells and hypergammaglobulinaemia. High IgE has been described in Atypical complete DiGeorge syndrome HLH é é é Congenital neutropaenia é é é Ataxia- telangiectasia N or low ê N or é ê 25% have hyper- IgM phenotype
4 Hypergammaglobulinaemia 1. Connective tissue diseases/inflammatory arthropathies: a. Rheumatoid arthritis b. SLE c. Sjogren s syndrome usually elevated IgG1 d. Adult- onset Still s disease e. Other mixed connective tissue disease, spondyloarthropathy, reactive arthritis, ADEM, dermatomyositis, polymyositis 2. Vasculitis: a. Takayasu arteritis b. Polyarteritis nodosa c. ANCA- associated d. Kawasaki disease 3. Autoinflammatory disease: a. CAPS, FMF, TRAPS b. Sweet syndrome c. JIA and Adult- onset Still s disease 4. Autoimmune liver disease a. Particularly autoimmune hepatitis b. Primary sclerosing cholangitis c. Primary biliary cirrhosis 5. Inflammatory bowel disease 6. Haematologic disease: a. ALL b. High- grade lymphomas c. CML d. Hodgkin lymphoma e. Graft- versus host disease post- transplant f. Neuroblastoma
5 g. Monoclonal gammopathy associated with plasma cell dyscrasias or lymphoproliferative disorders. h. Autimmune haemolytic anaemia, ITP 7. Non- autoimmune Liver disease a. Cirrhosis of any cause increases gammaglobulins due to the chronic inflammatory state/bacterial gut translocation 8. Infection a. Viral Hep B/C, HIV, EBV, CMV b. Bacterial SBE, osteomyelitis, TB c. Atopic dermatitis with superinfection d. Chronic sinusitis e. Chronic lung disease/cf f. Abscess g. Strep- associated: rheumatic fever, post- strep arthritis, post- strep GN, pneumonia, sepsis h. Brucellosis, Lyme disease, viral encephalitis Drug- associated: a. Acute drug hypersensitivity reaction b. Drug- induced autoimmunity 11. Solid organ malignancy 12. Other: a. IgA nephropathy b. Sickle cell anaemia c. Portal hypertension d. Lymphatic malformation
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