SERUM ANTIBODIES FROM PATIENTS WITH CROHN'S DISEASE AND FROM THEIR
HOUSEHOLD MEMBERS REACT WITH MURINE LYMPHOMAS INDUCED BY
CROHN'S DISEASE TISSUE FILTRATES.
Das KM; Simon MR; Valenzuela I; Weinstock JV; Marcuard SM; J Lab Clin Med, 1986 Jan,
107:1, 95-100

Injection into athymic nude mice (nu/nu) of filtrates of Crohn’s disease tissue produces lymphoid
hyperplasia and lymphomas, which react with serum antibody from other patients with Crohn’s
disease. We examined for such antibodies in sera of 14 patients with Crohn’s disease and 25 of their household members and compared results with sera from 36 healthy unselected controls and from
14 patients with ulcerative colitis and 19 of their household members. Sera from all patients with
Crohn’s disease and ulcerative colitis and household members were collected in Michigan, coded,
and examined by an indirect immunofluorescence assay against two primary nu/nu lymphomas and
one transmitted lymphoma produced by three Crohn’s disease tissue filtrates. Seven patients with
Crohn’s disease had antibodies against antigen(s) in the Crohn’s disease lymphomas. Seven household members of patients with Crohn’s disease and no household members of patients with ulcerative colitis (P less than 0.05) reacted with Crohn’s disease lymphomas. However, none of the patients with ulcerative colitis (P less than 0.01) and no control healthy subjects (P less than 0.005) demonstrated immunoreactivity against nu/nu lymphomas. None of the sera reacted with a control nu/nu lymphoma.  Five household members who had positive assay results were first-degree blood relatives, and the other two were spouses of patients with Crohn’s disease. These results suggest that a common environmental factor may be associated with Crohn’s disease, that there is a familial
association in Crohn’s disease, and that nu/nu mice are an important model to study the pathogenesis of Crohn’s disease.
 

LYMPHOCYTE REACTIVITY TO CROHN’S ILEAL HOMOGENATES.
Weinstock JV, Simon MR. J Clin Lab Immunol 1982 Nov;9(2):77-80

This study was undertaken to demonstrate whether lymphocytes derived from patients with Crohn’s disease and their household contacts would demonstrate increased reactivity upon exposure to tissue homogenates prepared from the terminal ileum of patients with Crohn’s disease. It was demonstrated that 4 of 18 patients, 9 of 30 household contacts, and 0 of 13 control subjects exhibited statistically greater lymphocyte thymidine incorporation in response to Crohn’s tissue homogenates (contacts vs control, P = 0.025) [Fisher Exact Test (FET)]. However, homogenates prepared from the terminal ileum of control subjects without inflammatory bowel disease also induced lymphocyte reactivity in 1 patient, 5 contacts, and 1 control subject. Factors may be present in homogenates prepared from human terminal ileum which induce lymphocyte reactivity in some patients with Crohn’s disease and household contacts.
 

KVEIM INDUCED LYMPHOCYTE REACTIVITY IN PATIENTS AND HOUSEHOLD
CONTACTS OF PATIENTS WITH CROHN’S DISEASE.
Simon MR; Weinstock JV; Kataria YP; J Clin Lab Immunol, 1980 May, 3:3, 175-8

In vitro lymphocyte thymidine uptake in response to validated Kveim antigen CR-1 was studied in
18 patients with Crohn’s disease and in 30 of their household contacts. Two of the patients and 3 of
the contacts demonstrated a stimulation index of 2 or greater. None of 15 control subjects
demonstrated such reactivity.  Lymphocytes from patient and household contact groups exhibited a greater mean increment in cpm than those from the control group (110, 130 and 33 cpm, respectively) (p < 0.05 and p < 0.005, respectively). This finding indicates a low level of lymphocyte reactivity to Kveim antigen in patients and in contacts, suggesting sensitization to Kveim antigen or to a cross-reacting antigen.
 

LYMPHOCYTOTOXIC ANTIBODIES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND THEIR SPOUSES—EVIDENCE FOR A TRANSMISSIBLE AGENT.
Strickland RG, Miller WC, Volpicelli NA, Gaeke RF, Wilson ID, Kirsner JB, Williams RC Jr. Clin Exp Immunol, 1977 Nov, 30:2, 188-92

Serum lymphocytotoxic antibodies (LCA) were detected in twenty-seven out of fifty-three (51%) patients with inflammatory bowel disease (IBD) and in twenty-three out of their fifty-three (43%) unaffected spouses. The prevalence of LCA in both groups was significantly increased (P less than 0.001) compared to that in age- and sex-matched controls (11%) or in control spouses (6%). Concordant expression of LCA occurred in sixteen out of the fifty-three (30%) patient-spouse pairs compared to only one out of the fifty-three (2%) control-spouse pairs (P less than 0.001). In contrast to the LCA results, heterophile antibody titres were similarly distributed in all four study groups. It is suggested that LCA may represent markers of infectious agents in IBD and that their occurrence in unaffected close contacts of patients may indicate transmission of such agents to these subjects.
 

LYMPHOCYTOTOXIC ANTIBODY IN INFLAMMATORY BOWEL DISEASE. A FAMILY STUDY.
Korsmeyer SJ; Williams RC Jr; Wilson ID; Strickland RG; N Engl J Med, 1975 Nov 27, 293:22,
1117-20

The prevalence of lymphocytotoxic antibody in inflammatory bowel disease is 40 per cent.
Twenty-seven of 90 relatives of 23 probands with the disease (30 per cent) demonstrated
lymphocytotoxic antibody, as contrasted with only three of 69 control family members (4 per cent)
(P less than 0.0001). Decreased lymphocytotoxicity against lymphocytes from patients with
inflammatory bowel disease as compared to normal donor lymphocytes previously demonstrated in
the serum of probands was also observed in the serums from family members of the probands.
Nineteen of the 48 household contacts of probands (40 per cent) were positive for antibody,
whereas eight of 42 nonhousehold contacts (19 per cent) demonstrated it (P less than 0.05). Eight of 16 spouses (50 per cent) of probands showed antibody. The increased prevalence of
lymphocytotoxic antibody in family members of probands and its occurrence mainly in household
contacts (consanguineous and non-consanguineous) may indicate the exposure of probands and their family members to a common environmental agent.