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Patients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris
Abstract
Objective. To determine if there is evidence of inflammation in the duodenal mucosa in patients with psoriatic arthritis (PsA) and to compare the results with those in patients with psoriasis vulgaris (PsV). Methods. Nineteen consecutive patients with PsA underwent gastroduodenoscopy, and biopsy specimens were taken from the duodenal and gastric mucosa. In addition to routine processing, the duodenal mucosal specimens were stained for CD3+, CD8+ and CD4+ T lymphocytes, tryptase-positive mast cells, and EG2-positive eosinophil granulocytes. The results were compared with those in duodenal mucosal specimens from patients with PsV and patients with irritable bowel syndrome. Results. Compared with PsV patients (without antibodies against gliadin), patients with PsA had a highly significant increase in intraepithelial CD3+ and CD8+ lymphocytes and also in CD4+ lymphocytes in the lamina propria in the villi. The lymphocyte increase was not related to presence of IgA antibodies against gliadin, endomysium, or transglutaminase, or to concomitant gastritis. Patients with PsA and PsV showed a pronounced increase in mast cells and eosinophil granulocytes. Conclusion. The increased lymphocyte infiltration in the duodenal mucosa in PsA, but not in PsV, might indicate different pathogenetic mechanisms in these psoriasis variants.
... All subtypes share clinical , radiological, and genetic characteristics evidently different from those of other chronic inflammatory joint diseases, for example rheumatoid arthritis. The presence of gut inflammation in psoriatic arthritis has been reported in several stud- ies63646566. In two of these studies it was observed that gut inflammation was only found in the forms of psoriatic arthritis belonging to the SpA concept, not in the polyarticular group. ...
Psoriatic arthritis is a chronic inflammatory joint disease, seen in combination with the chronic inflammatory skin disease psoriasis and belonging to the family of spondylarthritides (SpA). A link is recognized between psoriatic arthritis and inflammatory bowel disease (IBD). Environmental factors seem to induce inflammatory disease in individuals with underlying genetic susceptibility. The microbiome is a subject of increasing interest in the etiology of these inflammatory immune-mediated diseases. The intestinal microbiome is able to affect extra-intestinal distant sites, including the joints, through immunomodulation. At this point, evidence regarding a relationship between the microbiome and psoriatic arthritis is scarce. However, we hypothesize that common immune-mediated inflammatory pathways seen in the "skin-joint-gut axis" in psoriatic arthritis are induced or at least mediated by the microbiome. Th17 has a crucial function in this mechanism. Further establishment of this connection may lead to novel therapeutic approaches for psoriatic arthritis.
Introduction:
Plaque psoriasis and celiac disease are multisystemic diseases. The association of psoriasis and enteropathy with histological changes similar to celiac disease has already been described, and it has also been found that a gluten-free diet improves psoriatic changes. This study assesses the relationship between celiac disease antibodies and psoriasis.
Methods:
The study included 112 participants: 60 with psoriasis in a test group and 52 healthy subjects in a control group. Within the psoriasis group, participants were further divided into two subgroups: one consisting of patients with both psoriasis and psoriatic arthritis (n = 17) and another comprising patients with psoriasis alone (n = 43). After informed consent was obtained, the Dermatology Life Quality Index (DLQI) score and Psoriasis Area and Severity Index (PASI) score were evaluated. Laboratory tests included assessment of anti-deaminated gliadin peptide antibodies (DGP), anti-gliadin antibodies (AGA), and anti-tissue transglutaminase antibodies (tTG).
Results:
Immunoglobulin G (IgG) and immunoglobulin A (IgA) DGP antibodies were detected more frequently and at higher serum concentrations in patients with psoriasis compared to healthy controls (p = 0.03, p = 0.04, respectively). Similarly, elevated levels of IgG-tTG antibodies (p = 0.003) and IgA-DGP antibodies (p = 0.02) were observed in the same test group.
Conclusions:
A relationship between positivity to celiac disease antibodies and psoriasis, particularly with regard to AGA, has been identified. Further studies are required to elucidate the nature, pathophysiology, and significance of these findings.
Psoriasis is a symmetric autoimmune/inflammatory disease that primarily affects the skin. In a significant proportion of cases, it is accompanied by arthritis that can affect any joint, the spine, and/or include enthesitis. Psoriasis and psoriatic arthritis are multifactor disorders characterized by aberrant immune responses in genetically susceptible individuals in the presence of additional (environmental) factors, including changes in microbiota and/or epigenetic marks. Epigenetic changes can be heritable or acquired (e.g., through changes in diet/microbiota or as a response to therapeutics) and, together with genetic factors, contribute to disease expression. In psoriasis, epigenetic alterations are mainly related to cell proliferation, cytokine signaling and microbial tolerance. Understanding the complex interplay between heritable and acquired pathomechanistic factors contributing to the development and maintenance of psoriasis is crucial for the identification and validation of diagnostic and predictive biomarkers, and the introduction of individualized effective and tolerable new treatments. This review summarizes the current understanding of immune activation, genetic, and environmental factors that contribute to the pathogenesis of psoriatic arthritis. Particular focus is on the interactions between these factors to propose a multifactorial disease model.
The enhancer DNase-hypersensitive region 1,2 (HS1,2), a member of the Ig heavy-chain 3′ regulatory region (3′RR) cluster, is active in human B cells transfected with reporter genes and in mouse is activated in late maturation. HS1,2-A contains binding sites for several transcription factors. There are four known alleles, that is, *1, *2, *3, and *4, which differ in their lengths in transcription factor binding. We showed that in celiac disease the frequency of the *2 allele is increased. Both dermatitis herpetiformis (DH) and psoriasis can be associated with different frequencies with celiac disease. Thus, we further investigate the frequency of allele *2 in DH, plaque psoriatic, and psoriatic arthritis patients. HS1,2-A allele frequencies were investigated in 37 DH, 61 plaque psoriatic, 28 psoriatic arthritis patients, and 265 healthy donors, age- and sex-matched, from the same geographical area. The frequency of the *2 allele changes from 0.39 in controls to 0.63 in DH, 0.59 in plaque psoriasis and 0.75 in psoriatic arthritis (P between 10−4–10−5). Our data evidence an increased frequency of the *2 allele of HS1,2-A in these cutaneous immune-related disorders. We suggest a related genetic predisposition in these pathogeneses.Abbreviations: DH, dermatitis herpetiformis; HS, DNase-hypersensitive region; HS1,2-A, DNase-hypersensitive A region 1,2; 3′RR, 3′ Ig heavy-chain regulatory region; TGM, transglutaminase
Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei. Host factors likely predispose for the establishment of an infection, and macrophages seem to be involved in the pathogenesis of Whipple's disease. However, macrophage activation in Whipple's disease has not been studied systematically so far.
Samples from 145 Whipple's disease patients and 166 control subjects were investigated. We characterized duodenal macrophages and lymphocytes immunohistochemically and peripheral monocytes by flow cytometry and quantified mucosal and systemic cytokines and chemokines indicative for macrophage activation. In addition, we determined duodenal nitrite production and oxidative burst induced by T whipplei and by other bacteria.
Reduced numbers of duodenal lymphocytes, increased numbers of CD163(+) and stabilin-1(+), reduced numbers of inducible nitric synthase+ duodenal macrophages, and increased percentages of CD163(+) peripheral monocytes indicated a lack of inflammation and a M2/alternatively activated macrophage phenotype in Whipple's disease. Incubation with T whipplei in vitro enhanced the expression of CD163 on monocytes from Whipple's disease patients but not from control subjects. Chemokines and cytokines associated with M2/alternative macrophage activation were elevated in the duodenum and the peripheral blood from Whipple's disease patients. Functionally, Whipple's disease patients showed a reduced duodenal nitrite production and reduced oxidative burst upon incubation with T whipplei compared with healthy subjects.
The lack of excessive local inflammation and alternative activation of macrophages, triggered in part by the agent T whipplei itself, may explain the hallmark of Whipple's disease: invasion of the intestinal mucosa with macrophages incompetent to degrade T whipplei.
Both irritable bowel syndrome and inflammatory bowel diseases share symptoms of altered bowel habits associated with abdominal pain or discomfort. Irritable bowel syndrome has been referred to as a functional bowel disorder, which is diagnosed by a characteristic cluster of symptoms in the absence of detectable structural abnormalities. Inflammatory bowel disease is a heterogeneous group of disorders characterized by various forms of chronic mucosal and/or transmural inflammation of the intestine. In this review, the authors discuss recent evidence suggesting several potential mechanisms that might play a pathophysiologic role in both syndromes. Possible shared pathophysiologic mechanisms include altered mucosal permeability, an altered interaction of luminal flora with the mucosal immune system, persistent mucosal immune activation, alterations in gut motility, and a role of severe, sustained life stressors in symptom modulation. It is proposed that similarities and differences between the two syndromes can best be addressed within the framework of interactions between the central nervous system and the gut immune system. Based on recent reports of low‐grade mucosal inflammation in subpopulations of patients meeting current diagnostic criteria for irritable bowel syndrome, therapeutic approaches shown to be effective in inflammatory bowel disease, such as probiotics, antibiotics, and antiinflammatory agents, have been suggested as possible therapies for certain patients with irritable bowel syndrome.
In a screening study concerning IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA, respectively) in psoriasis, raised levels of IgA and AGA were found to be more common than in a reference group. To determine whether elevated AGA levels were associated with an increased number of intraepithelial lymphocytes. 33 patients with IgA AGA (n= 28) or IgG AGA (n= 5) values above 90% of the reference values (>50 units/ml IgA AGA and <12 units/ml IgG AGA) underwent gastroduodenoscopy and duodenal biopsy in a prospective study. For comparison, six patients with low levels of both IgA AGA and IgG AGA were included. Five biopsy specimens were taken in each patient. Paraffin-embedded specimens were examined with regard to the degree of intraepithelial lymphocyte infiltration, and scored from 0 to 3. Biopsy specimens with a score of 0 had one mononuclear cell or less per four epithelial cells. The specimens were also examined with regard to the presence of intraepithelial CD3⁺ T lymphocytes and γ/δ⁺ T lymphocytes.
Mast cells have been most extensively studied in their traditional role as an early effector cell of allergic disease. However, in the majority of individuals, it might be the role of this cell as a sentinel in host defense that is most important. Mast cells have been repeatedly demonstrated to play a critical role in defense against bacterial infections, and evidence for their involvement in early responses to viral and fungal pathogens is growing. Mast cells are activated during innate immune responses by multiple mechanisms, including well-established responses to complement components. In addition, novel mechanisms have emerged as a result of the explosion of knowledge in our understanding of pattern-recognition receptors. The mast cell shares many features with other innate immune effector cells, such as neutrophils and macrophages. However, a unique role for mast cells is defined not only by their extensive mediator profile but also by their ability to interact with the vasculature, to expedite selective cell recruitment, and to set the stage for an appropriate acquired response.
Mast cells (MCs) are major effector cells in allergic diseases. Recently, it has become evident that the contribution of MCs extends far beyond their accepted role in allergic disease, and that they play a more extensive role in a variety of non-allergic immune processes such as the innate immunity response. These cells have a key role in both the induction and elicitation of several autoimmune conditions. Targeting MC development, maturation or activation may be of value in future prevention and treatment of autoimmune conditions.