OP0267 REVERSE TRANSCYTOSIS IN ILEUM IS A MECHANISM WHICH COULD EXPLAIN THE HIGH LEVELS OF SERUM SECRETORY IgA IN SpA PATIENTS
Authors: J. De Avila, A. Ramos-Casallas, D. Acero-M, C. Florez, L. Parra, L. Chila, W. Bautista-Molano, A. Beltrán, D. Jaimes, J. M. Bello-Gualtero, C. F. Pacheco Tena, P. Chalem, C. Romero-Sánchez
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Previous results showed the apical expression of CD71 as a receptor associated with retrotranscytosis in ileum from SpA patients without inflammatory bowel disease (IBD) and its relationship with high levels of serum SIgA (sSIgA) and activity disease. The retrotranscytosis mechanism could explain the increases of sSIgA in SpA patients; however, this process has not been confirmed yet. <h3>Objectives:</h3> To confirm reverse transcytosis of SIgA through the ileum mucosa of SpA patients without inflammatory bowel disease. <h3>Methods:</h3> In total, 180 patients with SpA (ASAS/criteria) were assessed by rheumatologists, of which (n=65, 36.1%) met the selection criteria and from them (n=41, 63.1%) by a gastroenterologist to perform digital chromoendoscopy with magnification for colon e ileum and histological analysis. All included patients were between 18 and 65 years old, and those patients with SpA and concomitant IBD were excluded. CD71 by an in-house indirect immunofluorescence. In all patients who showed apical expression of CD71, proximity ligation assay (PLA) was performed to confirm the interaction of CD71-SIgA. CD71-SIgA complexes were followed through their co-localization with Rab-5, Rab-7 and Rab-11A. The analysis were made using the Chi-square or Fisher's exact test and a multiple correspondence discriminant analysis (MCDA). <h3>Results:</h3> The average age of the patients included was 44,6±10.2 years, 56.1% were men, 39.0% were HLA-B*27:05 positive, 90.2% had axial involvement. Serum levels of SIgA were 62.3±24.1 gr/mL, CRP 1.7±2.4 and ESR 14.1±12.0 mm/h. Positive levels of Fecal Calprotectin (FC) (&gt;120ng/mL) were observed in 31.7%. BASDAI &gt;4 was found in 58.5% of patients and ASDAS-CRP &gt;2.1 in 75.6%. Apical expression of CD71 was observed in 48.8% in ileum. CD71 expression was associated with high levels of sSIgA (p=0.05). The MCDA showed a reliability coefficient of 0.763 and showed a main dimension (Dim1) that collected serum sSIgA (CC 0.513), ASDAS-CRP &gt;2.1 (CC 0.311), CD71 (CC 0.424), and a secondary dimension (Dim2) related to the presence of loss of the vascular pattern in the ileum (CC 0.325), FC+diarrhea (CC 0.695), FC+abdominal distension (CC 0.883) and FC+abdominal pain (CC 0.885). The apical interaction complexes of CD71-SIgA in the ileum was demonstrated through PLA. Microscopic analysis showed that CD71-SIgA complexes were co-located with Rab-5 (in the apical side) and Rab-11A (in the basal side) but not with Rab-7 which is known to mediate transport to the lysosome. <h3>Conclusion:</h3> The results reveal that CD71-SIgA complexes are transported from the apical side of the epithelial barrier to the basolateral side in the ileum, confirming the reverse transcytosis of SIgA in patients with SpA. The positive correlation of CD71 in the ileum with sSIgA confirms retrotranscytosis as one of the mechanisms responsible for the high levels of SIgA in patients with SpA without IBD. These findings had not been reported before in SpA and reveal an important edge of the intestine-enthesis axis in these patients. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> The Ministry of Science, Technology, and Innovation - MinCiencias (Grants No. 68022 and 57442). Universidad El Bosque (PCI-2018-10300), Hospital Militar Central (Grant 2017-023), Clínicos IPS, Gastroadvanced, Fundación Instituto de Reumatología Fernando Chalem, in Bogota, Colombia and Biomedicina de Chihuahua, México. <h3>Disclosure of Interests:</h3> <b>None declared.</b>