Histological remission of ulcerative colitis with combined anti-cytokine and cell therapy

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Abstract

Aim. To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy.

Materials and methods. We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) – MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS).

Results. We determined medium correlation between basic FC and MS before treatment (r=0.6605, p<0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.8±2.1 mg/l, FC 409.3±44.85 µg/g, medium GS 1.2±0.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.4±1.4 mg/l, FC 435.5±47.3 µg/g, medium GS 1.35±0.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.4±1.1 mg/l, FC 290.6±17.5 µg/g, medium GS 0.9±0.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p<0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease.

Conclusion. Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission

About the authors

Oleg V. Knyazev

Loginov Moscow Clinical Scientific Center; Ryzhykh National Medical Research Center of Coloproctology; Research Institute of Health Organization and Medical Management

Email: asfold@mail.ru
ORCID iD: 0000-0001-7250-0977

д-р мед. наук, зав. отд-нием воспалительных заболеваний кишечника, проф. научно-образовательного отд., вед. специалист организационно-методического отд. по колопроктологии, вед. науч. сотр.

Russian Federation, Moscow; Moscow; Moscow

Sergey G. Khomeriki

Loginov Moscow Clinical Scientific Center

Email: asfold@mail.ru
ORCID iD: 0000-0003-4308-8009

д-р мед. наук, проф., рук. научно-исследовательского отд. патоморфологии

Russian Federation, Moscow

Anna V. Kagramanova

Loginov Moscow Clinical Scientific Center

Email: asfold@mail.ru
ORCID iD: 0000-0002-3818-6205

канд. мед. наук, ст. науч. сотр. отд-ния воспалительных заболеваний кишечника

Russian Federation, Moscow

Albina A. Lishchinskaya

Loginov Moscow Clinical Scientific Center

Email: asfold@mail.ru
ORCID iD: 0000-0001-7891-2702

канд. мед. наук, ст. науч. сотр. отд-ния воспалительных заболеваний кишечника

Russian Federation, Moscow

Olga A. Smirnova

Loginov Moscow Clinical Scientific Center

Email: asfold@mail.ru
ORCID iD: 0000-0002-0088-4075

мл. науч. сотр. лаб. нутрициологии

Russian Federation, Moscow

Karina K. Noskova

Loginov Moscow Clinical Scientific Center

Email: asfold@mail.ru
ORCID iD: 0000-0001-5734-0995

канд. мед. наук, зав. клинико-диагностической лаб.

Russian Federation, Moscow

Asfold I. Parfenov

Loginov Moscow Clinical Scientific Center

Author for correspondence.
Email: asfold@mail.ru
ORCID iD: 0000-0002-9782-4860

д-р мед. наук, проф., рук. отд. патологии кишечника

Russian Federation, Moscow

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2. Fig. 1. Moderate ulcerative colitis: a – dystrophy and desquamation of surface epithelial cells. Decrease of Goblet cells. Moderate infiltration of lamina propria, ×120; b – neutrophils between epithelial cells and destruction of crypts, ×500. Hematoxylin and eosin staining.

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3. Fig. 2. Correlation between FC and GS in UC patients before the treatment.

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4. Fig. 3. UC, remission: a – mild inflammatory infiltration of lamina propria. Increase of Goblet cells. Signs of chronic inflammation: deformation and splitting of end parts of the crypts, ×120; b – Paneth cell metaplasia, ×500. Hematoxylin and eosin staining.

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5. Fig. 4. Correlation between FC and GS in UC patients after 12 weeks of treatment.

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