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376 Suppression of murine IgE antibody responses to trimellitic anhydride
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POSITIVE PRAUSNITZ-KffSTNER REACTION IN METABISULFITE SENSITIVE SUBJECTS. W.H. Yang,M.D., E.C.R. R.N. Rivington,M.D.,Ottawa,Canada. Purchase,M.D., Sulfitine agents have been reported to cause abdomanaphylaxis, asthma, urticarialangioedema, inal pain & diarrhea. The pathogenesis of these reactions remain largely unknown. The possible role of IgE mediated mechanism has been debated. To better understand the pathogenesis, we studied Group (Gp) I 32 subjects with urticaria/ angioedema, Gp II 9 asthmatics, Gp III 8 headache all of them claimed to be & Gp IV 1 anaphylaxis; related to restaurant meals or alcoholic beverages; and 20 controls. Prick/intradermal (ID) skin testing using potassium metabisulfite (K2S2O5) lmg/ml were carried out on all subjects. Single blind oral challenge tests were carried out using placebo (lactose), K2S2O5 1,5,10,25 & 50mg in most subjects. Pulmonary function tests including FEVl & FVC were measured in Gp II. Five subjects had positive skin testing; 1 prick (Gp II), 4 ID (1 Gp I, 2 Gp II, 1 Gp IV) at lmg/ml. Passive transfer using unheated sera from K2S205 sensitive subjects was positive in 2 (1 Gp II, 1 Gp IV); heated sera (at 37°C for one hour) were negative. Four subjects developed adverse reactions upon oral challenge; one anaphylactoid reaction with generalized urticarialangioedema & hypotension (Gp IV),3 with acute asthmatic response with decline in FEVl of 38,50 & 68% at 5,25 & 50mg. We conclude that the positive P-K reaction, immediate onset reaction(anaphylactoid reaction & acute bronchospasm)following oral challenge test suggests that in selected groups of patients sensitive to K2S2O5, IgE mechanism do play a role. I
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DETECTION OF SULFITE RESIDUES IN RESTAURANT Ph.D., L. B. Martin and SALADS. S. L. Taylor, J. A. Nordlee, B.S., Madison, Wisconsin The use of sulfites on salads by restaurants can present a hazard to the sulfite-sensitive Sulfites are used to prevent the asthmatic. discoloration of salads and may be used on lettuce salad, cole slaw, fruit salad, potato This and other typical salad bar items. salad, study was undertaken to determine the levels of sulfite residues that might be expected in salads treated in this way, to assess the frequency of sulfite use in local restaurants, and to evaluate sulfite oxidase-impregnated test strips as qualitative indicators of sulfite use on salads. Lettuce treated with "salad freshener" according to label directions possesses 650950 ppm sulfite as SO2; most of the sulfite is present as free, inorganic sulfite. Sulfite levels remain unchanged through 24 h of refrigerated storage. When treated with excessive amounts of "salad freshener", the residual sulfite levels increased in a linear fashion. Cole slaw treated with sulfites according to a typical commercial formulation contained 250 ppm residual sulfite as SO2. A survey of restaurants in the Madison, WI area revealed 'chat O/12 lettuce samples, O/l3 cole slaw samples, and O/l2 potato salads were treated with sulfites. Sulfite oxidase-impregnated strips can be used to detect the use of sulfites in salads. The strips develop a red color when liquid shaken from lettuce is applied. The strips are commercially available and could be supplied to sulfite-sensitive asthmatics.
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METABISUL~(MBS)-ASSOCIATED PROTECTION BY HEPATOTOXICITY AND COBALAMINS (812). M Flaherty, MD, JM Stormont, MD, JJ Condemi, MD, Rochester, New York. We studied the relationshio between metabisulfite ingestion and hepatotoxicity in a 37 y.o. male with sclerosing cholangitis (SC). At age 15 ulcerative colitis (UC) was diagnosed. He was referred because of worsening liver condition and symptoms following ingestion of home-preserved juices and eating salad at a restaurant. Each episode was accompanied by palmer and plantor erythema with pruritis. LFT’s improved on an MBS-free diet. We then monitored LFT’s before and 2 days after a double blind oral challenge of 500mg MBS or lactosee placebo (PL). Challenges were separated by l-4 weeks to allow LFT’s to return to baseline. The patient was then rechallenged while on oral B12, 3mg. The results were: On B12 NoB12 No BS Post Post Post Post Free PL BS PL$;l2 “Z&F12 Diet SGOT 111 68 295 SGPT 197 170 112 12 156 649 ALK.P. 236 190 149 175 162 235 GGTP 684 428 3.88 698 558 477 We conclude that in this patient MBS ingestion resulted in the exacerbation of LFT and that this exacerbation could be prevented with B12. Additional patients with SC and other forms of liver disease will have to be studied in order to determine if this is a unique or more general phenomenon in SC patients and the role of the inflammatory bowel disease. In addition sulfite-oxidase levels should be determined to see if deficient activity is required for MBS induced hepatotoxicity.
SUPPRESSION OF MURINE IgE ANTIBODY RESPONSES TO TRIMELLITIC ANHYDRIDE. B.-Y. Wei, M.D., V. Holford-Strevens, Ph.D. and A.H. Sehon, Ph.D., Winnipeg, Manitoba, Canada. c, Antibodies of the IgE and other classes to the trimellityl group (TM) of the industrial chemical trimellitic anhydride (TMA) were induced in B6D2Fl mice by i.p. injection of TM-ovalbumin with Al(OH) as adjuvant. It was previously reported tha i administration of conjugates prepared by coupling TMA to the non-immunogenic polymer polyvinyl alcohol (PVA) suppressed the anti-TM IgE response. The present study has shown that this state of tolerance was maintained following adoptive transfer of spleen cells from TM-PVA treated mice into irradiated syngeneic recipients, which were subsequently immunized with TM-OA. The maintenance of the tolerant state of the transferred cells was not reversed by incubation ' *n vitro in tolerogen free medium, prior to cell transfer. Tolerance could also be induced ' ln vitro by incubating spleen cells from TM-OA primed mice with TM-PVA; when these cells were transferred into irradiated recipients, reduced secondary anti-TM responses were obtained. The persistent murine IgE response is known to be radiation resistant and insensitive to T suppressor cell regulation. A single dose of TM-PVA, given 18 weeks after primary immunization, almost completely suppressed the radiation resistant anti-TM response for at least 5 weeks. It is suggested that the suppression induced by TM-PVA conjugates may involve tolerization of B cells and blockade of antibody forming cells.
POSITIVE PRAUSNITZ-KffSTNER REACTION IN METABISULFITE SENSITIVE SUBJECTS. W.H. Yang,M.D., E.C.R. R.N. Rivington,M.D.,Ottawa,Canada. Purchase,M.D., Sulfitine agents have been reported to cause abdomanaphylaxis, asthma, urticarialangioedema, inal pain & diarrhea. The pathogenesis of these reactions remain largely unknown. The possible role of IgE mediated mechanism has been debated. To better understand the pathogenesis, we studied Group (Gp) I 32 subjects with urticaria/ angioedema, Gp II 9 asthmatics, Gp III 8 headache all of them claimed to be & Gp IV 1 anaphylaxis; related to restaurant meals or alcoholic beverages; and 20 controls. Prick/intradermal (ID) skin testing using potassium metabisulfite (K2S2O5) lmg/ml were carried out on all subjects. Single blind oral challenge tests were carried out using placebo (lactose), K2S2O5 1,5,10,25 & 50mg in most subjects. Pulmonary function tests including FEVl & FVC were measured in Gp II. Five subjects had positive skin testing; 1 prick (Gp II), 4 ID (1 Gp I, 2 Gp II, 1 Gp IV) at lmg/ml. Passive transfer using unheated sera from K2S205 sensitive subjects was positive in 2 (1 Gp II, 1 Gp IV); heated sera (at 37°C for one hour) were negative. Four subjects developed adverse reactions upon oral challenge; one anaphylactoid reaction with generalized urticarialangioedema & hypotension (Gp IV),3 with acute asthmatic response with decline in FEVl of 38,50 & 68% at 5,25 & 50mg. We conclude that the positive P-K reaction, immediate onset reaction(anaphylactoid reaction & acute bronchospasm)following oral challenge test suggests that in selected groups of patients sensitive to K2S2O5, IgE mechanism do play a role. I
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DETECTION OF SULFITE RESIDUES IN RESTAURANT Ph.D., L. B. Martin and SALADS. S. L. Taylor, J. A. Nordlee, B.S., Madison, Wisconsin The use of sulfites on salads by restaurants can present a hazard to the sulfite-sensitive Sulfites are used to prevent the asthmatic. discoloration of salads and may be used on lettuce salad, cole slaw, fruit salad, potato This and other typical salad bar items. salad, study was undertaken to determine the levels of sulfite residues that might be expected in salads treated in this way, to assess the frequency of sulfite use in local restaurants, and to evaluate sulfite oxidase-impregnated test strips as qualitative indicators of sulfite use on salads. Lettuce treated with "salad freshener" according to label directions possesses 650950 ppm sulfite as SO2; most of the sulfite is present as free, inorganic sulfite. Sulfite levels remain unchanged through 24 h of refrigerated storage. When treated with excessive amounts of "salad freshener", the residual sulfite levels increased in a linear fashion. Cole slaw treated with sulfites according to a typical commercial formulation contained 250 ppm residual sulfite as SO2. A survey of restaurants in the Madison, WI area revealed 'chat O/12 lettuce samples, O/l3 cole slaw samples, and O/l2 potato salads were treated with sulfites. Sulfite oxidase-impregnated strips can be used to detect the use of sulfites in salads. The strips develop a red color when liquid shaken from lettuce is applied. The strips are commercially available and could be supplied to sulfite-sensitive asthmatics.
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METABISUL~(MBS)-ASSOCIATED PROTECTION BY HEPATOTOXICITY AND COBALAMINS (812). M Flaherty, MD, JM Stormont, MD, JJ Condemi, MD, Rochester, New York. We studied the relationshio between metabisulfite ingestion and hepatotoxicity in a 37 y.o. male with sclerosing cholangitis (SC). At age 15 ulcerative colitis (UC) was diagnosed. He was referred because of worsening liver condition and symptoms following ingestion of home-preserved juices and eating salad at a restaurant. Each episode was accompanied by palmer and plantor erythema with pruritis. LFT’s improved on an MBS-free diet. We then monitored LFT’s before and 2 days after a double blind oral challenge of 500mg MBS or lactosee placebo (PL). Challenges were separated by l-4 weeks to allow LFT’s to return to baseline. The patient was then rechallenged while on oral B12, 3mg. The results were: On B12 NoB12 No BS Post Post Post Post Free PL BS PL$;l2 “Z&F12 Diet SGOT 111 68 295 SGPT 197 170 112 12 156 649 ALK.P. 236 190 149 175 162 235 GGTP 684 428 3.88 698 558 477 We conclude that in this patient MBS ingestion resulted in the exacerbation of LFT and that this exacerbation could be prevented with B12. Additional patients with SC and other forms of liver disease will have to be studied in order to determine if this is a unique or more general phenomenon in SC patients and the role of the inflammatory bowel disease. In addition sulfite-oxidase levels should be determined to see if deficient activity is required for MBS induced hepatotoxicity.
SUPPRESSION OF MURINE IgE ANTIBODY RESPONSES TO TRIMELLITIC ANHYDRIDE. B.-Y. Wei, M.D., V. Holford-Strevens, Ph.D. and A.H. Sehon, Ph.D., Winnipeg, Manitoba, Canada. c, Antibodies of the IgE and other classes to the trimellityl group (TM) of the industrial chemical trimellitic anhydride (TMA) were induced in B6D2Fl mice by i.p. injection of TM-ovalbumin with Al(OH) as adjuvant. It was previously reported tha i administration of conjugates prepared by coupling TMA to the non-immunogenic polymer polyvinyl alcohol (PVA) suppressed the anti-TM IgE response. The present study has shown that this state of tolerance was maintained following adoptive transfer of spleen cells from TM-PVA treated mice into irradiated syngeneic recipients, which were subsequently immunized with TM-OA. The maintenance of the tolerant state of the transferred cells was not reversed by incubation ' *n vitro in tolerogen free medium, prior to cell transfer. Tolerance could also be induced ' ln vitro by incubating spleen cells from TM-OA primed mice with TM-PVA; when these cells were transferred into irradiated recipients, reduced secondary anti-TM responses were obtained. The persistent murine IgE response is known to be radiation resistant and insensitive to T suppressor cell regulation. A single dose of TM-PVA, given 18 weeks after primary immunization, almost completely suppressed the radiation resistant anti-TM response for at least 5 weeks. It is suggested that the suppression induced by TM-PVA conjugates may involve tolerization of B cells and blockade of antibody forming cells.