| Full text | |
| Author(s): Show less - |
Genaro, Livia Moreira
;
Carron, Juliana
;
de Castro, Marina Moreira
;
Franceschini, Ana Paula Menezes de Freitas
;
Lourenco, Gustavo Jacob
;
da Cruz, Cristiane Kibune Nagasako Vieira
;
Reis, Glaucia Fernanda Soares Rupert
;
Pascoal, Livia Bitencourt
;
Mello, Juliana Delgado Campos
;
Pereira, Isabela Machado
;
Nascimento, Millene Leal
;
Oliveira, Priscilla De Sene Portel
;
Corona, Ligiana Pires
;
Ayrizono, Maria de Lourdes Setsuko
;
Lima, Carmen Silvia Passos
;
Leal, Raquel Franco
Total Authors: 16
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY; v. 39, p. 21-pg., 2025-01-01. |
| Abstract | |
Crohn's disease (CD) involves immune system interactions with intestinal tissue, driven by pro-inflammatory cytokines like Tumor Necrosis Factor (TNF-alpha). Adalimumab, targeting TNF-alpha, regulates associated inflammatory responses. Despite being humanized, it may induce immunogenic processes, affecting treatment effectiveness. Thus, monitoring serum adalimumab and anti-drug antibody (ADA) levels can optimize therapy. Understanding genetic factors influencing adalimumab response can enhance personalized treatment and improve patient quality of life. We aimed to quantify adalimumab serum levels, assess test interchangeability, detect ADA, examine immune complex formation, and investigate genetic phenotypes related to immunogenicity in CD patients. Seventy CD patients in the maintenance phase with adalimumab were classified into active (CDA) and remission (CDR) groups. Adalimumab concentration was determined via enzyme-linked immunosorbent assay (ELISA-Promonitor) and lateral flow assay (Quantum Blue), with assay interchangeability assessed statistically. ADA and immune complex formation were quantified using ELISA assays. DNA was genotyped for the genes ATG16L1, CD96, and CD155. No significant differences in adalimumab serum concentrations were observed between groups, regardless of the assay. However, a statistical difference between the tests indicated measurement disparity (P = 0.003), with moderate agreement (Lin's correlation of 0.247). ADA was detected in 4 of 27 of the patients with infratherapeutic levels, 3 in the CDA group and 1 in the CDR group. Analysis of immune complexes revealed significantly higher concentrations in the CDA group (P = 0.0125). The genotypic evaluation revealed significant associations for the CD96 CC (wild-type) genotype with higher CRP levels, colonic involvement, and infratherapeutic levels of adalimumab. ATG16L1 CC genotype was associated with higher CDEIS and fecal calprotectin values, while the variant (TT) genotype had lower platelet counts. The effectiveness of treatment with adalimumab was not directly related to higher medication levels in this cohort. The disparity between tests indicates the need to use only one test in patient follow-up to ensure accuracy in therapeutic monitoring. Genotypic differences highlight the correlation between the wild genotype for CD96 and ATG16L1 with unfavorable laboratory and endoscopic response to adalimumab. Finally, the more significant levels of immune complexes in the CDA group indicate an association with a worse response to adalimumab. (AU) | |
| FAPESP's process: | 21/04349-4 - Serum levels of Adalimumab and anti-Adalimumab antibodies in Crohn's Disease patients |
| Grantee: | Ana Paula Menezes de Freitas Franceschini |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 21/10265-8 - Cancer Theranostics Innovation Center (CancerThera) |
| Grantee: | Carmino Antonio de Souza |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 23/12810-9 - Evaluation of radiolabeled anti-integrin peptide modified by conventional chelator as a theranostic agent in glioblastoma |
| Grantee: | Juliana Carron |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/01924-5 - Evaluation of Adalimumab plasma levels and detection of anti-Adalimumab antibodies in patients with Crohn's Disease |
| Grantee: | Livia Moreira Genaro |
| Support Opportunities: | Scholarships in Brazil - Doctorate |