Functional Tests

The CH50 is a reliable and sensitive test for assessment of the classic complement pathway as a whole [64]. The CH50 represents the concentration of sample serum that lyses 50% of a standard cell suspension. Dilutions of the sample are incubated with a standard suspension of sheep erythrocytes in the presence of rabbit antibodies against sheep erythrocytes. The antibody solution has a standard concentration that lyses half of the cells in a given time in the presence of 1 ml of standard guinea pig complement (1 hemolytic or CH50 unit). If any of the classic pathway or terminal components are absent, the CH50 value will be 0 or extremely low.

A useful routine complement screen must include measurements of C3, C4 by immunochemical assays, and total hemolytic activity by CH50 assay.

3.2.1.7 HLA Typing

Histocompatibility leukocyte antigen (HLA) testing is of signiÞcance in a patient with episcleritis or scleritis and manifestations compatible with diseases that have shown speciÞc HLA association; these diseases include ankylosing spondilytis (HLA-B27), reactive arthritis (HLA-B27), Beh•etÕs disease (HLA-B51), and rheumatoid arthritis (HLA-DR4). SpeciÞc HLA positivity plays little or no role in the diagnosis of a disease because many HLA-B27, -B51, and -DR4 individuals in the general population remain unaffected, and these diseases may occasionally occur in individuals negative for HLA-B27, -B51, and -DR4 [65, 66]. Diagnosis is based on suspicion, history, clinical evaluation, or radiologic conÞrmation. For example, a patient with symptoms suggesting ankylosing spondylitis but with normal spinal radiographs does not have ankylosing spondylitis even if he/she is HLA-B27 positive (6% of normal Caucasians are HLA-B27 positive). In contrast, an HLA-B27-negative individual with sacroiliitis does have the disease (5Ð10% of Caucasians with ankylosing spondilitis are HLA-B27 negative). However, the presence of HLA-B27, -B51, and -DR4 increases the probability that the presumptive diagnosis is correct,

particularly when clinical and radiological Þndings are difÞcult to recognize with certainty. The combined use of HLA-B27 genotype and other factors enables adequate prediction of outcome resulting from anti-TNFa and conventional therapy in various ankylosing spondylitis subpopulations. This may help clinicians in making treatment decisions in daily practice [67].

3.2.1.8 Antibody Titers Against Infectious Organisms

The ßuorescent treponemal antibody-absortion test (FTA-ABS) and the microhemagglutination test for Treponema pallidum (MHA-TP) are sensitive tests for all stages of syphilis, except primary, early secondary, and early congenital forms. The FTA-ABS test is 98% sensitive and the MHA-TP test is 98Ð100% sensitive in tertiary syphilis [68Ð71]. The MHA-TP test is more speciÞc than the FTA-ABS test, with only 1% or less of positive reactions in rheumatoid arthritis, SLE, leprosy, relapsing fever, or yaws [70]. However, FTA-ABS or MHA-TP does not indicate active, as opposed to previous disease.

The ELISA for Borrelia burgdorferi antibodies is the most sensitive and speciÞc test for the diagnosis of Lyme disease; this ELISA is usually negative in stage 1, but is positive in 90% of patients in stage 2 and in almost 100% of patients in stage 3 [72]. The indirect ßuorescent antibody (IFA) method is also a reliable test.

Herpes zoster is readily diagnosed clinically in most instances. Occasionally, other diseases that can mimic herpes zoster may increase the possibility of misdiagnosis; in these cases, anti-varicella zoster virus (VZV) titers may be helpful. Initial VZV infection (chickenpox) produces cellular immune responses and IgG, IgM, and IgA antiVZV antibodies; [73] high levels of IgG anti-VZV persist throughout childhood. Recurrent VZV infection (herpes zoster) produces a rapid increase in antibodies to viral-associated membrane antigen, detectable by complement Þxation, ELISA, or IFA. Anti-VZV titers in herpes zoster are meaningful only when drawn as acute and convalescent sera about 1 month apart and demonstrate at least a twoto fourfold rise in titer. A single positive test