Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

Lima, Clara; Schroeder, John T.; Galvão, Clóvis Es; Castro, Fábio Morato; Kalil, Jorge; Adkinson, N. Franklin

doi:10.1590/s0100-879x2010007500096

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Ag (43,44), was not seen in piperacillin-hypersensitive patients, and this may relate to the absence of eosinophilia as a clinical feature. The detection of IL-1b, TNF-a, and IL-6 in culture supernatant containing piperacillin-stimulated PBMCs from hypersensitive patients and tolerant controls (albeit to a lesser extent) are suggestive of a dendritic cell response against piperacillin, as has recently been described with amoxicillin (45,46). In support of this argument, piperacillin-specific T cell clones do not secrete IL-1b (Sabah El-Ghaiesh, B. Kevin Park, and Dean J. Naisbitt, unpublished observations).…”

Section: Discussionsupporting

confidence: 52%

Mass Spectrometric Characterization of Circulating and Functional Antigens Derived from Piperacillin in Patients with Cystic Fibrosis

Whitaker

Meng

Lavergne

et al. 2011

The Journal of Immunology

142

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A mechanistic understanding of the relationship between the chemistry of drug antigen formation and immune function is lacking. Thus, mass spectrometric methods were employed to detect and fully characterize circulating antigens derived from piperacillin in patients undergoing therapy and the nature of the drug derived-epitopes on protein which can function as an antigen to stimulate T-cells. Albumin modification with piperacillin in vitro resulted in the formation of two distinct haptens, one formed directly from piperacillin and a second in which the dioxopiperazine ring had undergone hydrolysis. Modification was time- and concentration-dependent, with selective modification of Lys541 observed at low concentrations, whereas at higher concentrations up to 13/59 lysine residues were modified, four of which (Lys190, 195, 432 and 541) were detected in patients’ plasma. Piperacillin-specific T-lymphocyte responses (proliferation, cytokines and granzyme-B release) were detected ex vivo with cells from hypersensitive patients, and analysis of incubation medium showed that modification of the same lysine residues in albumin occurred in situ. The antigenicity of piperacillin-modified albumin was confirmed by stimulation of T-cells with characterized synthetic conjugates. Analysis of minimally-modified T-cell stimulatory albumin conjugates revealed peptide sequences incorporating Lys190, 432 and 541 as principal functional epitopes for T-cells. This study has characterized the multiple haptenic structures on albumin in patients, and showed that they constitute functional antigenic determinants for T-cells.

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Section: Discussionsupporting

confidence: 52%

Mass Spectrometric Characterization of Circulating and Functional Antigens Derived from Piperacillin in Patients with Cystic Fibrosis

Whitaker

Meng

Lavergne

et al. 2011

The Journal of Immunology

142

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“…Autoimmunity may also be triggered by drugs. DHR is classified as a type B drug reaction [17]. In fact, autoimmune-like diseases can emerge only in a small proportion of these patients [17].…”

Section: Discussionmentioning

confidence: 99%

“…DHR is classified as a type B drug reaction [17]. In fact, autoimmune-like diseases can emerge only in a small proportion of these patients [17]. However, we do not know how "biological" treatment applications, Covid 19 outbreak and widespread vaccination will affect this situation in increasing numbers and expanding indications.…”

Section: Discussionmentioning

confidence: 99%

İlaç alerjisi olan hastalarda otoantikor sıklığı

Altın

Değirmenci²

2022

Family Practice and Palliative Care

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Giriş: Bu çalışma, ilaç alerjisi olan hastalarda otoantikor sıklığını incelemeyi amaçlamaktadır. İlaç alerjisi üzerine gözlemsel araştırmalar, otoimmünite patofizyolojisi hakkında yeni hipotezlerin oluşturulmasına katkıda bulunabilir.Yöntem: Eğitim ve Araştırma Hastanesi veri tabanına 31 Aralık 2018 sonuna kadar kayıt olan ve ilaç alerjisi tanısı konan hastaların verileri geriye dönük olarak değerlendirildi. Genel olarak, ICD 10'a göre “ilaçlara alerji durumu” tanısı konan ve en az bir otoantikor sonucu olan 617 adet yetişkin hasta çalışmaya dahil edildi.Bulgular: Araştırmada en az bir otoantikora sahip olma sıklığı % 0 ile % 92,1 arasında değişti. En sık saptanan otoantikor romatoid faktör (RF) idi (n = 241; % 92,1). İkinci en sık rastlanan oto antikorun anti-doku transglütaminaz IgA (Anti-tTG-IgA) (n = 22; % 68,2) olduğu görüldü. Anti-tiroglobulin (Anti-TG), anti-tiroid peroksidaz (anti-TPO) ve anti-çift sarmallı DNA (Anti-dsDNA) sıklıkları sırasıyla % 65,2 (n = 155), % 59,7 (n = 159) ve % 43,6 (n = 55) olarak saptandı.Sonuç: Birçok ilaç, otoimmün hastalıkları için ilerleme olmaksızın otoantikor gelişimini tetikleyebilir. İlaçlara alerjisi olan hastalarda otoantikorlardan şüphelenilmesi gereklidir. İlaç alerjisi üzerine yapılan gözlemsel araştırmalar, otoimmünitenin patofizyolojisi hakkında yeni hipotezlerin oluşturulmasına katkı sağlayacaktır. Bu alanda yapılacak çok sayıda çalışma, riskli ilaçların yaygın kullanımını daha objektif bir şekilde tartışmamızı sağlayabilir. Çalışmamızın ilaç reaksiyonu ile otoimmün hastalıklar arasındaki ilişkiye ışık tutacağını düşünüyoruz.Anahtar kelimeler: Otoantikorlar, otoimmünite, ilaç alerjisi, ilaç aşırı duyarlılığı

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“…The pathogenic role of DC dysfunction (and its role as a potential therapeutic target) is the focus of continuing research, with descriptions of DC involvement in pathologic changes which have been associated with Th1/Th2 dysregulation, such as autoimmune disease (including rheumatic, neurologic and endocrine diseases [10–12], characterized by a Th1 response [13]) and allergy (including asthma, atopic dermatitis, and drug hypersensitivity [14–16], with a skew towards Th2 [13, 17]), and p Dc being implicated in diseases with a Type I Ifn -signature [18]. The rebalancing of Th1- and Th2-type responses, through Th2 stimulation in autoimmunity and Th1 shift in allergy, could be harnessed therapeutically [9, 19, 20].…”

Section: Dendritic Cellsmentioning

confidence: 99%

Dendritic Cells in Cord Blood Transplantation: A Review

Pereira

Paiva

2011

Stem Cells International

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Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells derived from hematopoietic progenitors that bridge the transition between the innate and adaptive immune responses, while maintaining self-tolerance and Th1/Th2 homeostasis, by priming other cells in either an immunogenic or tolerogenic direction. Through their role in both innate and adaptive immunity, DCs play a major part in transplant engraftment and rejection and in graft-versus-host disease (GvHD). Preferentially tolerogenic or immunogenic DC subtypes offer targets for immunotherapy, to optimize transplant success rates and prolong disease-free and overall survival. Cord blood DCs are immature and preferentially tolerogenic, due to maternal-fetal tolerance, leading to better graft acceptance and immune reconstitution and explaining the lower incidence and severity of GvHD in CB transplantation, despite donor-host mismatching. Manipulation of DC maturation and cell loading with tumor-antigens can direct antitumor immunity and target minimal residual disease, as demonstrated for acute myeloid leukemia, optimizing the graft-versus-leukemia effect.

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Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

Cited by 6 publications

References 14 publications

Mass Spectrometric Characterization of Circulating and Functional Antigens Derived from Piperacillin in Patients with Cystic Fibrosis

Mass Spectrometric Characterization of Circulating and Functional Antigens Derived from Piperacillin in Patients with Cystic Fibrosis

İlaç alerjisi olan hastalarda otoantikor sıklığı

Dendritic Cells in Cord Blood Transplantation: A Review

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