Article

Altered innate and adaptive immune responses in patients with hidradenitis suppurativa.

4th Department of Internal Medicine, Univeraity of Athens, Medical School, University General Hospital Attikon, 1 Rimini Street, 124 64 Athens, Greece.
British Journal of Dermatology (Impact Factor: 3.76). 02/2007; 156(1):51-6. DOI: 10.1111/j.1365-2133.2006.07556.x
Source: PubMed

ABSTRACT The clinical improvement of hidradenitis suppurativa reported in a small number of patients with antitumour necrosis factor (anti-TNF)-alpha therapies supports the hypothesis for an altered immune response in these patients.
To evaluate the state of the innate and adaptive immune responses in patients with hidradenitis suppurativa.
Fifty-three patients and six healthy controls were studied. Blood was sampled and subpopulations of lymphocytes were analysed by flow cytometry; monocytes were isolated and their function was evaluated from the concentrations of TNF-alpha and interleukin (IL)-6 in supernatants of cell cultures after triggering with endotoxins (lipopolysaccharides). TNF-alpha and IL-6 were estimated by an enzyme immunoassay.
CD3/CD8 lymphocytes were lower in patients with involvement of the perineum than in controls; patients with involvement of the breast had higher levels of natural killer (NK) cells than controls. A negative correlation was found between years lapsing since initial presentation of lesions of hidradenitis and the percentage of NK cells. Monocytes isolated from healthy volunteers were more active for the secretion of TNF-alpha and IL-6 than those of patients with hidradenitis suppurativa.
A reduction in the percentage of NK cells over time and a lower monocyte response to triggering by bacterial components is observed in patients with hidradenitis suppurativa. Further research is needed to clarify if these changes are connected to an autoimmune mechanism in the pathogenesis of hidradenitis suppurativa.

1 Bookmark
 · 
104 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antigen presentation in chronic skin disorders is mediated through the interleukin (IL)-12/IL-23 pathway and, hence, through the IL-12 receptor. Recent evidence suggesting dysregulated antigen presentation in skin lesions of hidradenitis suppurativa (HS) led to investigate the role of single nucleotide polymorphisms (SNPs) of the gene IL-12RB1 coding for the IL12-Rβ1 receptor subunit. Genomic DNA was isolated from 139 patients and 113 healthy controls; nine SNPs in the transcribed region of IL12RB1 were genotyped. No significant differences of genotype and allele frequencies were found between the two groups. Two common haplotypes were recognized, namely h1 and h2. Carriage of h2 related with minor frequency alleles was associated with a greater risk for the acquisition of Hurley III disease stage and with the involvement of a greater number of skin areas. Patients with the h1 haplotype presented disease at an older age. This is the genetic study enrolling the largest number of patients with HS to date. Although SNPs of IL12RB1 do not seem to convey genetic predisposition, they are associated directly with the phenotype of the disease.
    Cytokine 04/2013; · 2.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent findings in familial hidradenitis suppurativa (HS) demonstrated loss-of-function mutations of components of the γ-secretase (GS) complex leading to decreased protease cleaving activity, which may compromise canonical Notch signalling. Appropriate Notch signalling is of pivotal importance for maintaining the inner and outer root sheath of the hair follicle and skin appendages. This viewpoint on the pathogenesis of HS is primarily supported by circumstantial evidence derived from translational biology. Impaired Notch signalling is proposed to be the major pathogenic mechanism of HS. Deficient Notch signalling switches the fate of outer root sheath cells, resulting in conversion of hair follicles to keratin-enriched epidermal cysts. Impaired Notch signalling may compromise apocrine gland homoeostasis as well. Damage-associated molecular pattern molecules released by either ruptured epidermal cysts exposing keratin fibres or altered structural components of less maintained apocrine glands may both stimulate TLR-mediated innate immunity. All aggravating factors of HS, that is, smoking, obesity, skin occlusion, androgens and progesterone, may further promote inflammation by release of proinflammatory cytokines derived from activated monocyte/macrophages. Inappropriate Notch signalling may not only initiate inflammation in HS but may lead to insufficient feedback inhibition of overstimulated innate immunity. Regular Notch signalling via induction of MAPK phosphatase-1 (MKP-1) terminates TLR-MAPK-signalling in macrophages and IL-23 secreting DCs, the key players for Th17 cell polarization. Thus, impaired Notch signalling links HS to other Th17-driven comorbidities. All major therapeutic interventions in HS appear to attenuate increased MAPK activation of innate immune cells due to impaired Notch-mediated feedback regulation of innate immunity.
    Experimental Dermatology 03/2013; 22(3):172-177. · 3.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionHidradenitis suppurativa (HS) is a chronic skin disease which causes a great impact in the quality of life. Multiple therapeutic options have been proposed, and recently the potential use of biological drugs in severe cases has been postulated. Material and MethodsA retrospective study from seven tertiary Spanish centers reviewing the charts of patients with HS treated with biological drugs was performed. Retrieved information included epidemiological data, clinical features, pain intensity, Hurley stage, laboratory data and therapeutic outcomes. ResultsNineteen patients were included in the study; 10 men (52.6%) and 9 women. Eight patients (42%) showed a Hurley severity stage II and 11 a stage III (57.8%). Adalimumab was prescribed as the first biological treatment in nine out of 19 cases (47.3%), whereas infliximab was prescribed in seven cases (36.8%), ustekinumab in two cases (10.5%) and etanercept in one (5.2%). A complete response was observed in three patients (two cases with infliximab and one case with ustekinumab), a partial improvement in 10 patients and in six patients no clinical improvement was noted. One patient referred worsening of the skin symptoms. In 6 cases, a second biological treatment was prescribed. In three of such cases, a partial improvement was noted, whereas in three cases no clinical improvement was observed. In two cases a switch to a third biological drug was indicated, with a partial improvement in one case. Discussion and Conclusions Biological drugs could be a potential and effective therapeutic option for patients with severe HS. Complete and persistent clinical responses are rarely obtained (15%) and partial responses are achieved in approximately 50% of patients. No specific markers for a therapeutic response have been identified. No definitive conclusions regarding the most effective biological drug for HS could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude a potential efficacy to another biological treatment.
    Journal of the European Academy of Dermatology and Venereology 03/2014; · 2.69 Impact Factor