Perianal Crohn’s disease and hidradenitis suppurativa: a possible common immunological scenario

Abstract

BackgroundCrohn’s disease (CD) and Hidradenitis suppurativa (HS) are both chronic inflammatory diseases. The pathogenesis of these diseases is multifactorial, due to the interaction of genetic and environmental factors leading to a deregulated local immune response where T lymphocytes play a major role. To the best of our knowledge, no previous study has clarified whether the pathogenetic mechanism of perianal CD and HS is the same. We therefore analyzed the cellular expression pattern and the cytokine repertoire in three patients suffering from both perianal CD and HS.MethodsWe evaluated three patients affected by concurrent HS and CD with fistulizing perianal disease. Surgical specimens have been fixed and embedded in paraffin prior to sectioning for histological examination. Inflammatory tissue curettages have been recovered during intervention from perianal fistulas and HS lesions in order to analyze the phenotypic and functional characteristics of infiltrating T cells. In particular we evaluated T cells, by flow cytometry, for cytokine production profile and expression of surface markers. Moreover, analysis of the T cell repertoire was performed by means of spectratyping, in only one patient.ResultsA higher frequency of CD4+ CD161+ T lymphocytes has been detected in CD fistulas and in HS lesions than in peripheral blood (PB) samples. In the patient in whom we derived enough cells from the three sources, we found higher frequency of CD4+ IL-17- producing cells in HS lesion and fistula lesion compared to PB. It is noteworthy that the same clonotypes were expanded in this patient in T cells derived from both HS lesion and fistula lesion.ConclusionThe presence of numerous CD4+ CD161+ lymphocytes in fistula and HS lesion curettages suggests that these cells may play a pathogenic role, and candidates CD161 as a possible biological target for medical treatment.

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

“…14 Two recent studies reported a higher frequency of CD161+ CD4+ T lymphocytes in HS lesions. 15,16 Moran et al 16 demonstrated that the ratio of Th17 cells to CD4+ FoxP3+ CD127 low regulatory T cells (Tregs) in lesional skin was highly dysregulated in favour of IL-17 secreting Th17 cells. In lesional skin of patients with HS, increased levels of antimicrobial peptide LL-37 have recently been detected, which were associated with a Th1/ Th17 immune response.…”

“…CD161 is a specific surface marker of Th17 cells, indicating their exclusive origin from a CD161+ CD4+ T‐cell progenitor . Two recent studies reported a higher frequency of CD161+ CD4+ T lymphocytes in HS lesions . Moran et al .…”

Chitinase 3-like-1 is produced by human Th17 cells and correlates with the level of inflammation in juvenile idiopathic arthritis patients

“…CCR6 and RORc), in resting Th17 clones when compared to classic Th1. We and others already assessed that the frequencies of CD161+ Th17-derived Th1, Th17/Th1 and Th17/Th2, cells, positively correlated with severe phenotype of different chronic inflammatory disorders such as JIA, IBDs and asthma, respectively [31–36]. In the same pathological conditions higher levels of CHI3L1 have been detected in patients’ serum respect to healthy donors [14–16].…”

“…The Th17-derived Th1 cells expressed CD161, while the other Th1 cells present in the SF did not, and we named the former cells as non-classic, as compared with classic CD161− Th1 cells [33]. Moreover, we found an accumulation of Th17 and non-classic CD161+ Th1 lymphocytes in fistula curettage of patients suffering of fistulising Crohn’s disease [35, 36]. Another evidence of the high plasticity of human Th17 cells also emerges by the recent finding of the existence of a subset of human circulating memory CD4 T cells that produce both IL-17A and IL-4 [31].…”

MRI anatomy and pathology of the anal canal

“…59 The main differential diagnosis for HS is perianal fistulas associated with Crohn's disease: the two conditions may have overlapping imaging features, and at times may coexist. 57,60,63 Monnier et al showed that the fistulas in Crohn's disease are more complex and predominantly in the perianal region, with a slight increase in frequency of intersphincteric fistulas compared with HS. 58 In HS, the fistulas were more often bilateral and without associated rectal wall thickening.…”