Background The prevalence of IgE-mediated diseases has been increasing worldwide, yet IgE-expressing B cells are poorly characterized, mainly because of their scarcity and low membrane IgE levels. ...Objective We sought to study the immunobiology of human IgE-expressing B cells in healthy subjects and patients with allergic disease. Methods We used a stepwise approach for flow cytometric detection and purification of human IgE-expressing B cells in control subjects, CD40 ligand–deficient patients, and patients with atopic dermatitis. Molecular analysis of replication histories, somatic hypermutation (SHM), and immunoglobulin class-switching was performed. Results Using multicolor flow cytometry, we reliably detected IgE-expressing plasma cells and 2 IgE-expressing memory B-cell subsets. These IgE-expressing cells showed molecular and phenotypic signs of antigen responses. The replication history and SHM levels of IgE+ plasma cells and CD27+ IgE+ memory B cells fitted with a germinal center (GC)–dependent pathway, often through an IgG intermediate, as evidenced from Sγ remnants in Sμ-Sε switch regions. CD27− IgE+ cells showed limited proliferation and SHM and were present in CD40 ligand–deficient patients, indicating a GC-independent origin. Patients with atopic dermatitis had normal numbers of blood IgE+ plasma cells and CD27+ IgE+ memory B cells but increased numbers of CD27− IgE+ memory B cells with high SHM loads compared with those seen in healthy control subjects and patients with psoriasis. Conclusions We delineated GC-dependent and GC-independent IgE+ B-cell responses in healthy subjects and indicated involvement of the GC-independent pathway in a human IgE-mediated disease. These findings provide new insights into the pathogenesis of IgE-mediated diseases and might contribute to accurate monitoring of IgE+ B cells in patients with severe disease undergoing anti-IgE treatment.
Background and Aims:
Psoriasis and hidradenitis suppurativa HS co-occur more often with inflammatory bowel disease IBD than expected, due to shared pathogenic and genetic features. It is known that ...IBD patients harbour an altered intestinal microbiome characterised by a depletion of Faecalibacterium prausnitzii and increase of Escherichia coli. At present, it is unclear whether a similar intestinal microbiome trend can be identified in IBD-associated skin disorders. We therefore investigated the F. prausnitzii and E. coli abundance in psoriasis and HS, with and without concomitant IBD.
Methods:
Using quantitative polymerase chain reaction , we compared the F. prausnitzii and E. coli abundances in faecal samples from healthy controls n = 33 with samples from patients with psoriasis n = 29, IBD n = 31, and concomitant IBD and psoriasis n = 13. Likewise, we analysed samples from patients with HS n = 17, and concomitant IBD and HS n = 17.
Results:
Psoriasis patients harboured a significantly lower abundance of F. prausnitzii in their stool than healthy controls p < 0.001, which was similar to IBD patients. Together with the reduced F. prausnitzii levels, the psoriasis patients had a significantly higher abundance of E. coli p < 0.001. No significant difference in F. prausnitzii or E. coli abundance was found in HS. It was apparent that patients with concomitant IBD and associated skin disorder had the greatest decrease of F. prausnitzii and increase of E. coli.
Conclusions:
The study demonstrates, for the first time, an IBD-like decrease of F. prausnitzii together with an increase of E.coli in psoriasis, supporting the presence of a gut-microbiome-skin axis in psoriasis and IBD.
An acute hepatitis C virus (HCV) infection in an HIV-positive man who had sex with men (MSM) was notified. In the period of his seroconversion he was also diagnosed with a rectal lymphogranuloma ...venereum (LGV) infection, and was part of a cluster of 15 LGV cases in 2003. Our aim was to investigate HCV transmission and to search for potential spread among sexual contacts and known LGV patients.
Our case series included the index, two recent contacts, and 14 LGV cases. They were interviewed about parenteral exposure for HCV, history of sexually transmitted diseases(STDs), sexual behaviour and drug use. Laboratory investigations included anti-HCV antibodies, HCV-polymerase chain reaction, and HCV genotyping.
Seven out of 17 MSM recently seroconverted for HCV (41%). Three genotypes were found. Parenteral risk factors were excluded. Six out of seven had LGV proctitis coinciding with HCV seroconversion, six (86%) were HIV infected. Unprotected anal contact was practised by both HCV uninfected and infected cases. Unprotected active and passive fisting was reported by all seven HCV infected men, compared with two of nine uninfected men (P = 0.003). Non-intravenous drug use during sexual activities was common among all MSM. Numerous, often anonymous, sexual contacts in various European countries were reported.
A cluster of acute HCV infection is reported among mostly HIV-positive MSM, with multiple partners throughout Europe. Sexual techniques potentially leading to mucosal damage (fisting), concomitant STDs such as LGV and drug use seem facilitating factors for spread. Extensive case finding and partner tracing is advocated as well as targeted prevention messages.
Recent observations of abnormal immunoglobulin responses and case reports describing successful B-cell ablative therapy suggest involvement of B cells in the pathogenesis of sarcoidosis.
To ...investigate how abnormal B-cell maturation and function in patients with sarcoidosis contribute to disease.
Patients with sarcoidosis (n = 32) were included for detailed analysis by immunohistochemistry of tissue, flow cytometry of blood B-cell subsets, and serum immunoglobulin levels. Vaccination responses in patients with sarcoidosis to influenza virus and encapsulated bacteria and molecular analysis of immunoglobulin heavy chain transcripts were studied for functional analysis of immunoglobulin responses.
Perigranuloma localization of IgA-producing plasma cells and numerous B cells were found in affected tissues. Total blood B-cell numbers were normal, CD27(+) memory B cells were significantly reduced, and CD27(-)IgA(+) B cells were significantly increased; the results are normalized in patients treated with TNF-α blockers. Despite this, patients had normal serum immunoglobulin levels and normal antigen-specific immunoglobulin responses. IgA and IgG transcripts, however, showed high frequencies of somatic hypermutations and increased usage of downstream IgG subclasses, suggestive for prolonged or repetitive responses.
The large B-cell infiltrates in granulomatous tissue and increased molecular signs of antibody maturation are indicative of direct involvement of B cells in local inflammatory processes in patients with sarcoidosis. Moreover, CD27(-)IgA(+) B cells could be a marker for treatment with TNF-α blockers. These findings of B cells as emerging key players provide a rationale for a systematic study on B-cell ablative therapy in patients with sarcoidosis.
Psoriasis and inflammatory bowel disease (IBD) are chronic inflammatory diseases sharing similar pathogenic pathways. Intestinal microbial changes such as a decrease of bakers' yeast Saccharomyces ...cerevisiae have been reported in IBD, suggesting the presence of a gut-skin axis.
To investigate whether the S. cerevisiae abundance was altered in psoriasis patients versus healthy controls, and whether dimethylfumarate (DMF) interacted with this yeast.
Using qPCR, faecal samples were compared between psoriasis patients without DMF (n = 30), psoriasis patients with DMF (n = 28), and healthy controls (n = 32).
Faecal S. cerevisiae abundance was decreased in psoriasis compared to healthy controls (p<0.001). Interestingly, DMF use raised S. cerevisiae levels (p<0.001). Gastrointestinal adverse-effects of DMF were correlated with a higher S. cerevisiae abundance (p = 0.010). In vitro, a direct effect of DMF on S. cerevisiae growth was observed. In addition, anti-Saccharomyces cerevisiae antibodies were not elevated in psoriasis.
The abundance of baker's yeast S. cerevisiae is decreased in psoriasis patients, but appears to be restored upon DMF use. S. cerevisiae is generally classified as a yeast with beneficial immunomodulatory properties, but may also be involved in the occurrence of DMF's gastrointestinal adverse-effects. Potentially, DMF might be a new therapy for IBD.
...analyses and reproducibility in independent cohorts are necessary for proper understanding of disease pathology and for patient stratification to improve therapy success. ...we here analyzed the ...blood B-cell compartment of our previously published cohorts of patients with AD and patients with psoriasis.2 Within total CD19+ B cells, the naive, memory, and plasma blast subsets were classified by multicolor flow cytometry (Fig 1).2,5 In addition, IgM-only and immunoglobulin-class-switched memory B cells were defined within the IgD- events.
Background. Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) and is rare in the Western world. Recently, 3 men who have sex with men presented with LGV proctitis at the Erasmus ...Medical Center, Rotterdam, The Netherlands. We investigated a possible outbreak in a sexual network of men who have sex with men (MSM). Methods. After active case finding, a total of 15 men presented and were investigated. Serum antibody titers to Chlamydia trachomatis were determined. Urine and rectum specimens were analyzed by polymerase chain reaction (PCR) for the presence of C. trachomatis. C. trachomatis—positive specimens were genotyped to detect the specific C. trachomatis serovars. All subjects underwent routine STD screening. Sociodemographic, clinical, and endoscopic characteristics were evaluated. Results. Thirteen subjects had high immunoglobulin (Ig) G and IgA titers to C. trachomatis, suggesting an invasive infection. Rectal specimens of 12 subjects were PCR-positive for C. trachomatis. All urine specimens were negative. Genotyping revealed serovars L2 (n = 8) and L1 (n = 1). An ulcerative proctitis was found in all subjects obtaining sigmoidoscopy (n = 9). Eleven of 13 subjects with an LGV diagnosis were seropositive for human immunodeficiency virus (HIV), 6 had another concomitant STD, and 1 had recently acquired a hepatitis C virus infection. Further sexual contacts were reported from The Netherlands, Germany, Belgium, the United Kingdom, and France. Conclusions. We revealed an outbreak of LGV proctitis among MSM in The Netherlands. The ulcerous character favors transmission of HIV, other STDs, and blood-borne diseases. From a public health perspective, it seems important to increase the awareness of possible LGV in MSM with symptomatic proctitis.
The Microbiome and Psoriatic Arthritis Eppinga, Hester; Konstantinov, Sergey R.; Peppelenbosch, Maikel P. ...
Current rheumatology reports,
03/2014, Letnik:
16, Številka:
3
Journal Article
Recenzirano
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.
Diabetes mellitus (DM) is one of the common metabolic disorders, and a major part of chronic diseases, the prevalence of which tends to increase due to multifactor. Blood vessels, kidneys, lungs, and ...skin are among the organs that are affected. The first problem that arises, or commonly exists among one-third of diabetics, are problems with their skin, although skin lesions may develop along with the progress of the disease, or can occur during the later phase of DM. The prevalence and symptoms of skin problems in type 1 DM (T1DM) and type 2 DM (T2DM) are often unclear, and at the beginning of the course of the diseases they often go undiagnosed. Several theories regarding the pathophysiology of DM can be used as a logical reference for the early identification and diagnosis of skin problems, aimed at preventing the worsened condition. The use of skin autofluorescence (SAF) and AGEs reader in several cases of skin problems, can also be an important marker as an adjunct to predict the possibility and progressiveness of DM. Skin problems linked to patients with DM can be categorized as strongly related to diabetes, non-specific and related to DM, skin infection in DM, and skin problems due to diabetic medication. With the current COVID-19 pandemic, there are additional demands for more critical investigation of skin problems in patients with DM. The skin problems that occur in DM may need to be examined from the early stage and it is necessary to inhibit the progression of skin problems, as well as to consider the need for multidisciplinary DM therapy.
PDF
