Serum proteins in ulcerative colitis: electrophoretic patterns in the inferior mesenteric artery and vein.

Abstract

EDITORIAL COMMENT. These studies suggest that there is a local production or release of alpha 2 globulins and a fixation or destruction of gamma globulin by the diseased colon.Previous studies have indicated that in patients with severe attacks of ulcerative colitis, changes occur in the levels of the serum proteins. These changes consist principally of a fall in the serum albumin level, and a rise in the level of the alpha 2 globulins (Bicks, Kirsner, and Palmer, 1959;Brooke, Dykes, and Walker 1961;Soergel and Ingelfinger, 1961).Furthermore attacks of ulcerative colitis which fail to respond to conservative treatment are almost invariably accompanied by a low level of serum gamma globulin (de Dombal, 1967).However, these studies have done nothing to indicate the mechanisms responsible for the observed serum protein changes. In further investigations, therefore, the electrophoretic patterns have been compared in samples of blood removed at operation from the inferior mesenteric artery and the inferior mesenteric vein. Nineteen patients have been thus studied: a group of 10 patients with severe ulcerative colitis and a control group of nine patients with rectal or colonic cancer. CLINICAL MATERIAL AND METHODSBetween 1 March and 31 August 1966, a group of 10 patients were brought to radical surgery because of severe attacks of ulcerative colitis which were unresponsive to conservative treatment. At operation, immediately after the abdomen was opened, the inferior mesenteric vessels were identified and isolated. A sample of blood was then removed from the inferior mesenteric artery and a further sample from the inferior mesenteric vein. Both of these vessels were then ligated and divided in the usual manner. The samples of blood were then centrifuged and the serum was pipetted off. Total protein and albumin levels were determined using a routine Biuret method; and electrophoresis was carried out for each of the two samples using cellulose acetate membrane. Results have been expressed as g. % and each result is the mean of two entirely separate estimations which were performed on each individual sample.A further group of nine control patients with colonic cancer were studied; in seven of these patients blood was removed from the inferior mesenteric artery and vein and analysed by the same method. In the remaining two patients with a right-sided carcinoma of the colon, blood was removed from the appropriate right colic artery and vein and was again analysed in an identical manner.

Aetiology of ulcerative colitis.

“…However, recent studies in our own department have confirmed Broberger and Perlmann's findings in vivo, and they indicate that immune gamma globulin is fixed in the colon in the living colitis patients (de Dombal, 1967).…”

Aetiology of ulcerative colitis. II. A new hypothesis.

“…When at admission to hospital during an acute attack the patient's y-globulin levels were raised, and/or rising, remission occurred. However, when the level of y-globulins was low and falling, the patient invariably had to proceed to surgery (de Dombal, 1967b). These findings powerfully support the view that y-globulins can play a defensive role.…”

“…Outpatients in remission who were free from infectious and incidental diseases such as influenza and bronchitis were chosen for study. Fifteen patients with levels of a2-globulin above the normal range suffered an acute attack within three months, while 35 patients with normal or diminished a2-globulin levels suffered no such attacks (de Dombal, 1967b). When at admission to hospital during an acute attack the patient's y-globulin levels were raised, and/or rising, remission occurred.…”

“…Similarly, the specific a2-globulin fraction(s) showing an increase before acute attacks has (have) yet to be determined. Studies on the concentrations of serum proteins taken from the inferior mesenteric artery and vein of patients with severe attacks of ulcer-ative colitis have shown that a2-globulins are synthesized locallywithin the colon (de Dombal, 1967a). From the literature of related autoaggressive diseases, it has been tentatively suggested that mast cells might be involved, directly or indirectly, in the synthesis of primary a2-globulin 'autoantibodies' (Burch and Burwell, 1965;Burch, 1968).…”

Ulcerative colitis: definition, historical background, aetiology, diagnosis, naturel history and local complications

“…But this argument was in part refuted by their further studies (Perlmann & Broberger, 1963) showing that the leucocytes from patients with ulcerative colitis had a cytotoxic effect upon the foetal colon cells in tissue culture, an effect which was inhibited by pre-treatment with colon antigen. Broberger & Perlmann's pioneer work has recently been confirmed and extended (Fink, Donnelly & Jablokow, 1967;Watson, Quigley & Bolt, 1966;de Dombal, 1967).…”