Influence of intravenous immunoglobulin therapy on serum levels of anti-beta 4 antibodies in ocular cicatricial pemphigoid. A correlation with disease activity. A preliminary study.
OBJECTIVE
To determine any correlation between activity of ocular cicatricial pemphigoid and titer of anti-beta 4 antibodies, and any effect of intravenous immunoglobulin (IVIg) therapy on serum levels of anti-beta 4 antibodies followed over a 12 month period, using the specific immunoblot assay (IBA).


METHODS
Eight patients diagnosed with OCP and treated with IVIg as monotherapy were included in the study. Each patient was treated with at least two immunosuppressive agents prior to the institution of IVIg. The presence of anti-beta 4 antibodies in the patients' sera was detected by IBA using bovine gingival lysate (BGL) or tumor cell line lysate (TCL) as substrates. The activity of OCP was graded based on the conjunctival injection using a scale of zero to four in increments of 0.5 at monthly intervals. To determine the correlation between serum levels of circulating autoantibody and the patients' conjunctival disease activity, the titer of anti-beta 4 antibodies was determined at monthly intervals during the course of IVIg therapy. Blood samples were drawn prior to administration of IVIg infusion. The titer was determined by IBA, using serial dilutions of the patients' sera. The highest dilution at which the binding was visible was considered the titer. The dose of IVIg administered was approximately 2-3 g/kg/cycle. The infusion cycles were initially given at monthly intervals, approximately 70 grams daily over four hours for three consecutive days. As clinical improvement was observed, the interval between the cycles was increased, but the dose of IVIg remained the same for each cycle. To study whether the IVIg has an effect on other antibodies, monthly serum levels of antibodies to tetanus toxoid were measured by ELISA.


RESULTS
We observed a continuous decrease in mean monthly titer of circulating anti-beta 4 antibodies in the patients' sera during IVIg therapy. A decrease in conjunctival inflammation during the course of IVIg was documented by monthly examination in every patient and paralleled the decrease in titer of anti-beta 4 antibodies. Since the fifth month of IVIg therapy, the mean conjunctival inflammation remained less than 0.5, suggesting a clinical remission of OCP. Titers of antibodies to tetanus toxoid remained unchanged during the study period.


CONCLUSIONS
This preliminary study demonstrates a correlation between serum titers of anti-beta 4 antibodies and clinical disease activity in patients with OCP. In addition, the study shows that the use of IVIg is associated with a decrease in the serum titer of anti-beta 4 antibodies.
Letko
E
E
Department of Ophthalmology, Uveitis and Immunology Service, The Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02115, USA.
Bhol
K
K
Foster
S C
SC
Ahmed
R A
RA
D000368:Aged; D000818:Animals; D000906:Antibodies / Q000097:blood*; D015703:Antigens, CD / Q000276:immunology*; D002417:Cattle; D005128:Eye Diseases / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D016756:Immunoglobulins, Intravenous; D039663:Integrin beta4; D008297:Male; D008875:Middle Aged; D010390:Pemphigoid, Benign Mucous Membrane / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D012720:Severity of Illness Index; D013745:Tetanus Toxoid / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D016756:Immunoglobulins, Intravenous; D039663:Integrin beta4; D013745:Tetanus Toxoid