Test Via Disease

Investigation of Suspected Immunodeficiency

Primary immunodeficiencies are rare but need urgent investigation, especially in the case of young children to identify those with life threatening immunodeficiency status (e.g Severe Combined Immunodeficiency). Secondary immunodeficiencies are more common and may be due to infection (e.g. HIV) , malignancy ( e.g. myeloma or lymphoma), or the treatments for these malignancies, immunosuppressive therapy, malnutrition, or severe renal or hepatic disease. Below is a schematic guide to categories of immune deficiency and suggested tests required.

Investigations of Angioedema

Discussion with an immunologist advised.

Hereditary angioedema (HAE) is rare: estimated prevalence 1:50,000. It results from lack of C1 esterase inhibitor protein (C1-INH) in up to 85% of cases (type I HAE). In type II HAE C1-INH levels are normal but its functional activity is reduced¹. Rare cases of HAE with normal C1-INH levels and function have been described and mutations have been identified in subsets of these including in the genes encoding Factor XII and plasminogen². Acquired angioedema (AAE) is also rare. AAE type I is most commonly associated with B-cell lymphoproliferative disorders. AAE type II is an autoimmune process defined by the presence of an autoantibody directed against C1-INH.

Urticaria is NOT a feature of C1-INH deficiency (HAE/AAE). See testing algorithm below.

More common causes of angioedema include Angiotensin converting enzymes (ACE) inhibitors and spontaneous/idiopathic angioedema where urticaria may be an additional feature.

Gompels et al. Clinical and Experimental Immunology 2005; 139(3): 379-394. DOI: 10.1111/m.1365-2249.2005.02726.x
Bork et al. Allergy 2017: 1-9. DOI: 10.1111/all123270

Diagnosis of Myeloma

NICE guideline [NG35] Myeloma: Diagnosis and management recommends the following laboratory investigations for people with suspected myeloma:

Serum protein electrophoresis and serum‑free light‑chain assay to confirm the presence of a paraprotein indicating possible myeloma or monoclonal gammopathy of undetermined significance (MGUS).
If serum protein electrophoresis is abnormal, use serum immunofixation to confirm the presence of a paraprotein indicating possible myeloma or MGUS.
Serum protein electrophoresis, serum immunofixation, serum‑free light‑chain assay or urine electrophoresis (urine Bence–Jones protein assessment) should not be used alone to exclude a diagnosis of myeloma.

Recommended laboratory investigations to provide prognostic information include

Serum‑free light‑chain assay and serum‑free light‑chain ratio.

Suggested testing algorithms for other clinical conditions

Disease	Relevant Investigations
Addisons Disease	Adrenal antibodies
Allergy	IgE, Allergen specific IgE (RAST)
Anti-phospholipid syndrome	Anti-cardiolipin antibodies Anti-B2GP1 Lupus anti-coagulant (Haematology)
Autoimmune Hepatitis (Chronic Active Hepatitis)	Anti smooth muscle antibodies Anti-Liver kidney microsomal antibodies Anti-mitochondrial antibodies Anti-nuclear antibodies
Bullous skin disorders	Skin reactive antibodies Immunohistology (Histopathology*) Coeliac serology
C1 Esterase Inhibitor deficiency	Cl inhibitor, C3, C4
Chronic Granulomatosis Disease	Neutrophil function test
Chronic lymphatic leukaemia	serum protein electrophoresis Leukocyte phenotyping (Haematology*)
Coeliac Disease	Anti tissue transglutaminase antibodies
Congenital Heart Block	ANA (Anti-Ro)
Connective Tissue diseases	ANA
Cryoglobulinaemia	Cryoglobulins C3, C4
Dermatitis Herpetiformis	anti tissue transglutaminase antibodies
Dermatomyositis (anti-synthetase syndrome)	ANA (Anti-Jo- 1)
Diabetes	Anti-islet cell antibodies Anti-GAD antibodies
Discoid Lupus Erythematosus	Anti-nuclear antibodies Immunohistology (Histopathology*)
Fibrosing Alveolitis	Anti-nuclear antibodies
Glomerulonephritis	Immunohistology (Histopathology*) Anti-neutrophil cytoplasmic antibodies (ANCA) Anti-glomerular basement membrane antibodies (GMB)
Graves Disease	Anti-TSHR antibodies
Guillain-Barre Syndrome	Anti-peripheral nerve antibodies
Hashimotos Disease	Anti-TPO antibodies
Hereditary Angioedema	Cl esterase inhibitor (Cl INH) C3. C4
Infection	C reactive protein (Biochemistry) Immunoglobulins
Juvenile Chronic Arthritis	Anti-nuclear antibodies(IFA HEp2) C-reactive protein (Biochemistry) CCP
Latent TB	Quantiferon TB Gold
Leukaemia/Lymphoma	Leucocyte phenotyping (Haematology*)
Lupus anti-coagulant	Anti-phospholipid antibodies
lymphoproliferative disorders	Serum protein electrophoresis Immunofixation, serum free light chains, urine Bence Jones Protein. Leucocyte phenotyping (Haematology*) Cryoglobulins
Membranoproliferative glomerulonephritis (MPGN)	C3 C4 C3 Nephritic Factor
Microscopic Polyangiitis	Anti-neutrophil cytoplasmic antibodies
Mixed Connective Tissue Disease (MCTD)	Anti-nuclear antibodies (Anti-ENA antibodies if ANA positive)
Monoclonal Gammopathy	Serum protein electrophoresis Immunofixation Urine Bence Jones Protein
Multiple Sclerosis	CSF oligoclonal banding
Myasthenia Gravis	Anti-Acetylcholine Receptor antibodies
Myeloma	Serum protein electrophoresis Immunofixation Urinary Bence-Jones protein Serum free light chains
Non-Hodgkins lymphoma	Serum protein electrophoresis Leucocyte phenotyping (Haematology) Lymph node biopsy (Histopathology) Urinary Bence-Jones protein
Pernicious Anaemia	Anti-gastric parietal cell antibodies Anti-intrinsic factor antibodies
Pemphigus Pemphigoid	Immunohistology (Histopathology*) Skin Reactive antibodies
Polymyositis (anti-Synthetase syndrome)	ANA (Anti-Jo- 1)
Polyangiitis with granulomatosis (Wegener’s)	ANCA
Premature ovarian failure	Anti-adrenal antibodies
Primary Biliary Cirrhosis	Anti-mitochondrial antibodies
Rheumatoid Arthritis	Rheumatoid Factor C-reactive protein (Biochemistry) CCP ANA
Sjogren’s Syndrome	Anti-nuclear antibodies (Anti-Ro Anti-La)
Systemic Lupus Ervthematosus	Anti-nuclear antibodies Anti-DNA antibodies Anti-ENA antibodies Anti-cardiolipin antibodies C3 C4 C-reactive protein (Biochemistry)
Systemic Sclerosis (Scleroderma) Diffuse	ANA (anti-Scl-70)
Systemic Sclerosis (Scleroderma) Limited Cutaneous	ANA (anti-Centromere)
Vasculitis	Anti-neutrophil cytoplasmic antibodies ANA (Radiology/biopsy*) C-reactive protein (Biochemistry)
Waldenstroms Macroglobulinaemia	Immunoglobulins Serum protein electrophoresis Urinary Bence Jones Protein (Haematology/Histopathology*)