Clinical Laboratory - Chemical Pathology and Immunology


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Immunology

Autoimmune Diseases

Below are some of the most prevalent autoimmune deficiencies with the frequency of their expected autoantibodies. In any one patient, multiple factors go into the diagnosis of autoimmunity, not just laboratory results.

Autoantibody SLE SS RA Scl PM/DM
ANA 99% 68% 16 - 50% 40 - 75% 50 - 90%
dsDNA 70% 1 - 5% 1% - - - -
Smith 30% 1 - 5% 1% <1% <1%
SSA 25 - 35% 10 - 70% Low - - Low
RNP 50% 5 - 50% 5% 20% - -
Scl-70 - - - - 5% 20 - 60% - -
RF 15 - 35% 75 - 95% 50 - 90% 20 - 30% - -
CCP - - - - 40 - 70% - - - -
Jo-1 - - - - - - - - 30 - 50%

SLE = systemic lupus erythematosus; SS = Sjogren syndrome; RA = rheumatoid arthritis; Scl = systemic sclerosis (scleroderma); PM/DM = polymyositis/dermatomyositis

Complement Levels

Complement components most often measured include C3 and C4. Both C3 and C4 are acute phase proteins that, if elevated, may be related to inflammation or infection. Decreased levels may be seen with autoimmune disease, bacteremia, tissue injury, chronic hepatitis, and nephritis. Decreased levels are characteristic for systemic lupus erythematosus (SLE), disseminated antigen-antibody complex disease, acute glomerulonephritis, or chronic hepatitis. There are rare congenital complement deficiencies.

Increased C2 levels are associated with the acute phase response. C2 deficiency has been associated with increased susceptibility to infection, particularly S. pneumoniae infections, arthritis, rashes, and nephritis.

A C1q binding assay is used to detect circulating immune complexes, since C1q can recognize Fc on immunoglobulins.

Vasculitides

A positive antinuclear antibody test (ANA) is helpful to determine if the underlying disease is autoimmune, such as systemic lupus erythematosus (SLE).

The antineutrophil cytoplasmic autoantibody (ANCA) tests help in diagnosis of vasculitis. Both myeloperoxidase (MPO) and proteinase-3 (PR3) can be obtained. An example is ANCA-associated vasculitis with necrotizing granulomatous inflammation in multiple organs, particularly lungs and kidneys.

A simple sedimentation rate (sed rate) is non-specific for many types of inflammation, but a very high sed rate in conjunction with specific findings such as a tender temporal artery can be highly suggestive of giant cell arteritis.

Lymphocyte Immunophenotyping

This is generally performed via flow cytometry to enumerate peripheral blood lymphocyte populations. Of circulating lymphocytes, about 70% are T cells, 20% B cells, and 10% NK cells.

Of circulating T cells, there are generally more CD4 than CD8 cells, so that the CD4:CD8 ratio is > 1.

T cells have CD3 on their surface; they have T cell receptors (TCR) that recognize specific antigenic sequences presented to them. There are two main subsets: CD8 cells - restricted to MHC class 1 antigenic interaction; known as "suppressor cells" that have a cytotoxic effect; CD4 cells - restricted to MHC class 2 antigenic interaction; known as "helper cells" because they assist in antigen processing and stimulation of immune responses.

B cells have CD19 and CD20 on their surfaces. They have surface immunoglobulin that is specific for particular antigenic sequences. Fully differentiated immunoglobulin producing B cells are known as plasma cells.

NK cells are "natural killer cells" that are part of the innate immune response and react to stimuli that are not antigen specific. They can express CD11 and CD12 on their surfaces.


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