Our group has a long-standing interest in Helicobacter pylori (Hp) and its enzyme urease, and the pulmonary inflammation which occurs following micro-aspiration of Hp and its byproducts. We have established an animal model in which urease was delivered intratracheally via an osmotic pump for 1 month. Histopathology showed prominent peribronchial germinal centers and, in vitro analysis of urease showed cross-reactivity with a well-known lymphocyte mitogen, Concanavalin A (ConA). Urease, in a non-acidic milieu, increases in ConA reactivity as shown by Western blot. (ATS report 2004, Langdon and Herndon). With the hypothesis that enigmatic pulmonary inflammation may relate to aspiration of urease/ConA or its bacterial source, antibody capture was performed on the sera of fourteen subjects with sarcoidosis. We have previously reported that subjects with sarcoidosis often have high levels of antibody against Hp, as did these 14 (93%).
Eight 2x dilutions of the 14 serum samples were analyzed for specific IgG on microtiter plates coated with one of three capture antigens: Hp, urease, or ConA. Serum titer was the log10 mean dilution producing linear antigen binding. ConA (a putative breakdown product of urease) was analyzed on the subjects divided by Hp and urease reactivity: High Hp responders, low Hp responders, high urease responders, and low urease responders.
All 14 subjects with sarcoidosis had elevated antibody titers to both Hp and urease when plated against ConA. The subjects who were high urease responders showed a signigicant increase in ConA reactivity compared to subjects who were high Hp responders, p<0.02, student t-test. Our schematic interpretation of these results is: urease <zpi;•>“pH related breakdown <zpi;•>” ConA-like mitogen <zpi;•>” pulmonary inflammation <zpi;•>“ disease (and antigenic recognition).
Patients with sarcoidosis have a high immunologic response to a breakdown product of urease that has known mitogenic pulmonary effects in animals. The relationship to the etiology of their disease is unknown at this time.
Data providing evidence for the etiology of sarcoidosis would be a major advance in medicine.
C.D. Langdon, None.