230 Abstracts J. ALLERGY I.L;i’; !MMClhUi.

.iANLIA\RY 1991

361 HYPERSENSITIVITY TO TRICHOSANTHIN IN HIV-INFECTED PATIENTS. Abba I. Terr, M.D. ~ Jeffrev Davidson, M.D., and Roger Willzams, M. D. Stanford University School of Medicine and

363 QUANTITATION OF SULFAPIETHOXAZOLE-HUMAN SEKUM ALSUHIN (SlfX-WA) IgE ABTXBODIES IN HIV+ SUBJECTS. MA Reed, W Lopez, E Gutierrz& HysLop, and CE O’Neil. New Orleans, LA

Genelabs Incorporated, tiedwood City, CA. Trichosanthin is a basic non-glycosylated 27

kD single chain ribosome inactivating protein extracted from the tubers of Trichosanthes kirilowii Maxim. A highly purified form (>95% by HPLC), GLQ223”, is now under investigation for treatment of HIV infection.

In a Phase I safety/tolerance trial in ARC or AIDS, 48 subjects received up to 16 doses of GLQ223” intravenously at up to weekly intervals. During either the 3rd or 4th dose, 4 patients developed signs and symptoms of immediate hypersensitivity, including angioedema, urticaria, erythema and 1 subject developed hypotension . Manifestations in 3 of the 4 subjects were consistent with systemic anaphylaxis. Three had wheallflare on skin test with 5-50 rig/ml GLQ223”, 3 manifested igG and IgM antibodies, and 3 had IgE antibody by RAST. Only 1 of 7 treated controls had a positive skin test to 5000 nglml, and l/37 treated controls developed IgE antibody by RAST. Two controls with negative skin test and RAST to GLQ223” had delayed urticaria. The frequency of IgG and IgM antibodies to GLQ223’ and CD4+ cell counts were comparable in the 4 reactive patients and controls.

Immediate hypersensitivity with systemic manifestations to GLQ223” intravenously occurs with an incidence of 5-10% in ARC or AIDS and is mediated by IgE antibody.

362

Newark, N.J. Anttbodies (Abs) induced by SYX bound to albumtn

(SfbtX-HSA) form immune oomptexee and oeuse the development of the ‘SSX’ seen in SD-loo% of mV(+) as

.compsrul to ont 4% among HlV&) peifeMe (ptn). We evatueted HtV{+) SMXt+)(nG) for the preseneo of Aba ;7 agslnst SMX+lSA by ouohtertony, immwtolrtot, and EUSA Preolptttnrformed In l/3. tmmunebk&e detected IgO & tgA Atm mgainsl tlm SIX-H&% (but net HSA atone) In 3/3. Thwo wtm no btndtng In umptes from normal pts. ELtSA deteoM tgQ d tgM Aba @nst SMX-HSA whtch tnorensed from the basettna 8srum samples (taken b8fore S&+X Mrapy) to thefr hetght in serum semptes taken durtw the %8X nrotkmr (0.0.; 0.441 VI) 2.312: 0.362 vn 1.284: 0,802 w 2.223). Besetlne tgG btrtdtng to SMX-HSAtn 3 lUV(MSX+) had a mean 00, of 0.402 + .103 (Xwam). nw(+xlSX~-) (me) had a beuotine fg0 to SMX-ffSA of .233 +.C#B. In a campetltpW ILISA, tnoubstton with tncrosal~ concentrettons of SMX prwy decreased the OD,, readfn$& In a compcltithn ELlSA ee~y system, tnoubdion of one of HtV(+) pt wtth hutmeetng concentrattons of SMX progrewlvety deereaeed the 00, resdlngs. hlml~ with athor asJlf* bsmd ;sty; ~I$IcS~~ wlhdiadne, wmte,

tfamamk- and wllsnylurea dtd not oom~tvefy lnkibtt blndtnp and rest&d in OD rondhfp elmtier to beaaltne.

ias@ LINE PEAK 1 mdml 10 mg/ml 0.362 1.2a4 0.632 0.472

Incubetion wlth other eutfa baaed rrompounda e.g. sulfauuusde, depwne, did not wm@@My IMbtt binding and reedtad In 00, read@@ atmttar to buntline. This su@@aW that we ere abla to quMwltlvety cWWr)wtISc QjQ mdbadba wbfch mey medi8ta SMX reaction8 In Att5S pts.

There is a high incidence of advkrw reactions to trimethoprim-sulfamethoxazoic (T/S) in HIV+ patients. To assess ~~ potential

role of IgE antibodies, total IgE leiTc?is (K/ml), and SMX-HSA IgE antiboai.ec !:: Fiounc! were quantitated by RIA and RAST, rsapectiveiy. The study population comprised 49 R!.\i-. controls

(Grl); 26 asymptomatic HIV+ (Gr2) [hC’?G !>i9!: 23 late ARC or AIDS patients (Gr3; jhCTC OHi!. and 17 AIDS patients receiving treat.ment with T/S--divided into reactors (n=5; Gr4> a:id non-reactors (n=12; GrS). Mean log total ;gi, levels were different among the groups (p<O.OOOl), and increased with increasing tilt: disease severity. The X of indivj.duals with total IgE >lOO IU/ml also differed among the groups (p=O.OOOl): 30.6% (Grl), 34.6% (GrZ), 47.8% (Gr3), and 94% (Grs 4 4 51. ?ksn 7: bound also i.ncreased significantly with dxsease severity: 0.43 + 0.12 (Grl), 0.53 ,r 0+!)4 (Gr21, 0.79 + 0.16 (Gr3), 1.12 ; 0.33 (Gr4!: ;.33 1’ 0.25 TGrS, (p<0.0001). .n ail gruu+. totai and specific IgE leveis were lineasa:.y correlated. In Grs G and 5, thc!D. :Jf“:il ani>

differences between mean total IgE levels <llSb

T 915.6 and 1360 + 619.4) or meal? ‘? bound. We

hypothesize that elevated % bound t(i SMX-HSA in HIV+ patients are related to tota: :gh‘ leve?s. which in turn depend on disease sczvcr;t!‘. SMX-HSA antibodies were not corrr~k~lx~d wit?; adverse reactions to T/S.