Demonstration of Circulating Antinuclear Globulins in Ulcerative Colitis*

Abstract

Although Andresen (1) first considered "allergy" as a factor in the pathogenesis of ulcerative colitis in 1925, the recent studies of Levine, Kirsner, Klotz and Elchlepp (2-4) have renewed interest for the role of hypersensitivty in this disorder. Various clinical features suggest the presence of an altered immune state in ulcerative colitis. Among these are sensitivity to drugs and blood transfusion (5), the beneficial effects of ACTH and corticosteroids (6) and such extracolonic manifestations as erythema nodosum (7), uveitis (8), hepatitis (9, 10), myocarditis (6), glomerulitis (5, 11), arthritis (12-14), purpura (5) had previously undergone colectomy for this disorder. Four patients were studied before and after colectomy and are included in both groups. Over 300 sera from normal subj ects and from patients with various disease states were tested while the study was in progress.Whenever multiple tests were performed, aliquots of the same serum sample were used. All sera were stored at -200 C.Fluorescent antiglobulin tests. The details of the technique used have been reported previously (20). Briefly, the test sera were superimposed for 1 hour on: 1) normal human peripheral blood smears fixed in 95 per cent ethanol (20), and on 2) nucleohistone spots prepared from calf thymocytes (22, 23). The slides were thoroughly washed and fluorescein-labeled rabbit antihuman -y-globulin, absorbed with rat liver powder, was then used as a histochemical stain for human y-globulin. The first procedure tests the affinity of the sera for human leukocyte whole nuclei and the fluorescent label is detected by ultraviolet microscopy. In the second method, the sera are tested against calf nucleoprotein and fluorescence is visible to the naked eye when the slides are exposed to the beam of a Woods lamp.Lupus erytheniatosus (LE) cell preparations. The technique used was a variation of the Zinkham-Conley method (24). One ml of heparinized normal blood was added to 0.5 ml of test serum. After standing at room temperature for 2 hours with occasional shaking, 1.5 ml of the mixture was transferred to screw-top tubes containing glass beads and rotated at 40 rpm for 30 minutes at 370 C. The contents were then centrifuged in smallbore tubes to isolate the buffy coat which was smeared on glass coverslips, stained with Wright-Giesma and examined microscopically for the presence of LE cells.Rheumatoid

Autoantibodies in primary sclerosing cholangitis

“…In UC patients, antibodies against nuclear antigens were reported by Calabresi et al in 1961 [41] and Nielsen et al in 1983 (granulocyte specific-ANA) [42] . In PSC such antibodies were reported by Snook et al in 1989 [43] .…”

Zirkulierende antinukleäre Globuline bei der Colitis ulcerosa

“…Calabresi u. M itarb. [4] haben mit Hilfe der Immunofluoreszenzmethode im Serum an Colitis ulce rosa E rkrankter die Anwesenheit eines mit dem Zellkern reagierendes Globulin nachgewiesen. Ein Globulin, welches sich mit einem isolier ten Nukleoprotein verbindet, konnten sie nicht feststellen.…”

“…• 1 Das Globulin mit Affinität zum isolierten Nukleoprotein haben wir zum Unterschied von amerikanischen Autoren [4] bei 27% der K ran ken, wenn auch bei niedrigen Titerw erten (maximal 1:32) und zwar in direktem Zusam m enhang mit der K rankheitsaktivität, festgestellt. Die Bewertung der Unterschiede ist wegen der beschränkten Anzahl der Untersuchungen erschwert und kann von der Verschiedenheit der zur Bestimmung und zur Isolation des Nukleoproteins benutzten Me thoden beeinflußt sein.…”

“…Das erhöhte Vorkommen des antinukleären Faktors bei den Familienangehörigen der Kranken mit ulzeröser Koli tis [6] läßt erkennen, daß man die Ansicht Calabresis u. M itarb. [4], nach welchen es sich um eine genetisch bedingte Proteinabnorm alität handeln könne, welche einen immunologisch abweichenden Typus der Reaktivität begleitet oder indiziert, akzeptieren kann.…”

Cutaneous Hypersensitivity to Deoxyribonucleic Acid (DNA) in Patients with Ulcerative Colitis

“…Some have described in patients with systemic lupus erythematosus (SLE) a positive skin response to DNA [4,11]. Since the presence of circulating globulins with affinity for leukocyte or tis sue nuclei has been reported in a significant number of patients with ulcerative colitis [1,2,8,17] and their relatives [17], we decided to study a skin response to DNA and circulating DNA antibodies in our patients with ulcerative colitis.…”