su.45. longitudinal evaluation of ctl responses and hiv sequence evolution in optimally described...
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Su.45. Longitudinal Evaluation of CTL Responsesand HIV Sequence Evolution in OptimallyDescribed HIV-1 CTL Epitopes During Acute/EarlyHIV-1 InfectionQuentin Eichbaum,1 Brian Block,1 Zabrina Brumme,1
Hendrik Streeck,1 Jonathan Jolin,1 Heiko Jessen,2 BruceWalker.1 1MGH, Charlestown, MA; 2Jessen-Praxis, Berlin,Germany
Introduction: Cytotoxic (CD8+) Tcell (CTL) responses playa key role in the immune response to acute HIV infection butcontrol of viremia is compromised by viral escape mutations.In this study, we investigate CTL immune responses and viralsequence evolution longitudinally in the first year of infectionin a cohort of acutely infected HIV individuals. Methods:Following high resolution HLA typing, CTL responses wereassessed by IFN-γ ELISPOT assay on longitudinal samplestaken from eight acutely-infected treatment-naïve HIVindividuals over a median period of 45 weeks in the firstyear of infection. HIV sequencing of the Gag, Pol and Nefepitopes was performed on virus derived from the plasma ofthese samples. Results: CTL responses increased over thefirst year of infection and corresponded with a generaldecrease in HIV viremia. The earliest targeted epitopescorresponded with known HIV immunodominance responsesand these responses persisted. HIV epitope sequencingrevealed that all eight individuals had at least one instanceof sequence evolution in a defined Gag, Pol or Nef HLA-1restricted epitope (median 2.5 mutations/individual). Sevenindividuals had a mutation in Nef, whereas only two hadmutations in Gag and Nef epitopes. Two-thirds of escapemutations occurred in epitopes targeted at some stage byCTLs during this period. In three cases, mutations resulted inpartial to complete loss of epitope recognition. Conclusions:Our study confirms that HIV-specific CTL responses increaseduring acute/early HIV infection but that HIV adapts robustlyto this immune response through escape mutations.
doi:10.1016/j.clim.2008.03.396
Immuno-dermatology
Su.46. Involvement of Ig Heavy Chain HS1,2-AEnhancer ⁎2 Allele in Dermatitis Herpetiformis,Plaque Psoriasis and Psoriatic ArthritisFranco Pandolfi,1 Rossella Cianci,1 Vincenzo Giambra,2
Claudia Mattioli,2 Maria Esposito,3 Giovanni Cammarota,1
Grazia Scibilia,4 Giuseppe Magazzù,4 Ambrogio Orlando,5
Serena Lolli,1 Giancarlo Sandri,6 Lucia Bianchi,3 DomenicoFrezza.2 1Catholic University of Rome, Rome, Italy; 2TorVergata University, Rome, Italy; 3Tor Vergata UniversityHospital, Rome, Italy; 4University Hospital, Messina, Italy;5V. Cervello' Hospital, Palermo, Italy; 6S. Eugenio Hospital,Rome, Italy
Background: The enhancer HS1,2, member of the 3′regulatory region (3′RR) of the Ig heavy chain cluster,contains binding sites for several transcription factors.There are 4 known alleles, i.e. ⁎1, ⁎2, ⁎3 and ⁎4, respectively,
which differ in their lengths. We previously showed that inCeliac Disease (CD) the frequency of ⁎2 allele is increased.Both Dermatitis Herpetiformis (DH) and Psoriasis can beassociated with different frequencies with CD, we furtherinvestigate the frequency of allele ⁎2 in DH, Plaque Psoriaticand Psoriatic Arthritis patients. Patients/Methods: HS1,2-Aallele frequencies were investigated in 37 DH, 61 PlaquePsoriatic, 28 Psoriatic Arthritis patients and 265 healthymatched donors, from the same geographical area. Results:The frequency of the ⁎2 allele changes from 0.39 in controlsto 0.63 in DH, 0.59 in Plaque Psoriasis and 0.75 in PsoriaticArthritis (P between 10-4 - 10-5). Conclusions: Our dataevidence an increased frequency of the ⁎2 allele of HS1,2-Ain these cutaneous immune-related disorders. Furthermore,our preliminary data indicate an increased frequency ofHS1,2 allele ⁎1 in patients with selective IgA-deficiency.Taken together these data suggest that frequencies of HS1,2alleles may have a role in the onset of several diseasescharacterized by abnormal IgA production. It is relevant thatin this pathology where it takes place an increase of the ⁎1allele frequency is present a depletion of IgA productionwhereas in the pathologies showing IgA increased levels likeBerger disease and CD it is present an increase of the allele ⁎2.
doi:10.1016/j.clim.2008.03.397
Su.47. Analysing Skin-infiltrating T LymphocytesFrom a Patient with a Chronic InflammatoryGVHD-like DiseaseLaurent Méric de Bellefon,1 Anne Theunis,2 Jeannine deMaubeuge,2 Olivier Michel,3 Michel Goldman,1 FlorenceRoufosse,4 Pierre Coulie.5 1Université Libre de Bruxelles,Brussels, Belgium; 2Saint-Pierre Hospital, Brussels,Belgium; 3Brugmann Hospital, Brussels, Belgium; 4ErasmeHospital, Brussels, Belgium; 5Université Catholique deLouvain, Brussels, Belgium
A young male developed a systemic immune-mediateddisorder reminiscent of chronic graft-versus-host disease(GVHD), characterized by lymphocytic inflammation oflungs, small bowel and skin, after exposure to vinylchloride. Nineteen years later, the disease remains par-tially controlled by chronic immunosuppressive therapyassociating low-dose corticosteroids and azathioprine.Maternal microchimerism is suspected to play a role inthe disease given the presence of circulating XX cells in thepatient's blood, and the HLA class II near identity (5/6identical alleles) with his mother. Numerous attempts todemonstrate patient's T cell reactivity against maternalhaematopoietic cells (EBV transformed B cells) have provenunsuccessful. Analysis of skin sections revealed keratino-cyte necrosis, focal basal membrane disruption and Tlymphocyte infiltration. CD4+ and CD8+ T cell clones couldbe derived from chronic skin lesions and were tested forrecognition of maternal EBV-B cells. No cytokine secretionor lysis was observed. We also excluded that these T cellclones were of maternal origin. Considering the possibilitythat Tcell clones derived from skin lesions contribute to thedisease, our primary objective is to identify their antigens.We will explore the possibility that autologous keratinocytes
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