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Background: Cutaneous T-cell lymphomas (CTCL) are a group of rare non-Hodgkin lymphomas characterized by initial localization of malignant Tlymphocytes in the skin. Support and information from nurses and patient support groups have proven useful for patients with CTCL, but little is known about the educational needs of these patients. Objectives: To investigate the self-reported educational needs among CTCL patients using an educational needs assessment tool and to explore differences related to sex, age, disease duration, clinical stage, and education. Methods: This observational single center study analyzed 70 patients with CTCL in routine dermatological outpatient care. The patients were asked to complete a questionnaire to capture their educational needs in regard to CTCL. The questionnaire was inspired by the educational needs assessment tool, designed and validated for patients with rheumatoid disease. The questionnaire included a general question, "In general, how much information do you want to receive about your lymphoma disease?", and five domains covering information relating to disease process (6 items), treatment (4 items), feelings (2 items), self-management of itch, sleep, and rest (2 items), and support systems (3 items). The domain scores ranged from 0 to 18 and the total score from 0 to 51, with a higher score indicating a greater need for education. Results: When asked "In general, how much information do you need?", females wanted to know more compared with males (2.6 vs. 2.1, p=0.006), and patients with higher education wanted to know more than patients with lower education (2.5 vs. 2.0, p=0.025). The domains concerning treatment (80%) and disease process (75%) revealed the greatest needs for education. Patients with a disease duration <2 years reported a greater educational need for the domain support system, compared with patients with longer disease duration. Patients with lower education reported a greater educational need about feelings compared with patients with higher education. Conclusions: We found that 65% of the CTCL patients in the cohort, particularly females, expressed a need for education, especially regarding disease process and treatment. A deeper understanding of the educational needs would enable healthcare providers to give personalized information. [ABSTRACT FROM AUTHOR]

Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand the pathophysiology in XLN and the role of WASp in neutrophils, we here examined XLN patients and 2 XLN mouse models. XLN patients had reduced myelopoiesis and extremely low blood neutrophil number. However, their neutrophils had a hyperactive phenotype and were present in normal numbers in XLN patient saliva. Murine XLN neutrophils were hyperactivated, with increased actin dynamics and migration into tissues. We provide molecular evidence that the hyperactivity of XLN neutrophils is caused by WASp in a constitutively open conformation due to contingent phosphorylation of the critical tyrosine-293 and plasma membrane localization. This renders WASp activity less dependent on regulation by PI3K. Our data show that the amplitude of WASp activity inside a cell could be enhanced by cell-surface receptor signaling even in the context in which WASp is already in an active conformation. Moreover, these data categorize XLN as an atypical congenital neutropenia in which constitutive activation of WASp in tissue neutrophils compensates for reduced myelopoiesis., Introduction Severe congenital neutropenia (SCN) is characterized by low absolute neutrophil count in blood that leads to life-threatening infections and requires administration of granulocyte CSF (G-CSF) to stimulate the number [...]

Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease with kidney inflammation, lupus nephritis (LN), being one of the most severe manifestations. Immune complex deposits, particularly in glomeruli, and T cells, B cells, and myeloid cells, mainly with extraglomerular localization, contribute to the inflammatory process. Natural killer (NK) cells have been suggested to play a role in autoimmune diseases, but have not been investigated in detail in renal lupus before. In this exploratory study, we performed the first characterization of NK cell number and distribution in LN kidney biopsies. Twelve SLE patients were analyzed in the active phase of disease and five patients following immunosuppressive therapy. CD56+ cells, corresponding to NK cells or NK-like T-cells, were identified in all patients; however, with reduced numbers in four out of five patients at follow-up. Furthermore, cells were present in the kidney interstitium and peri-glomerular areas, but only rarely in glomeruli. Fluorescent co-staining of CD56 or NKp46 and CD3 revealed the presence of both CD56+/NKp46+CD3-NK cells and CD56+/NKp46+CD3+NK-like T-cells. Compared to healthy kidney sections, one out of four LN patients showed increased numbers of NK cells. A correlation between CD56+ and NK cells with clinical parameters could not be observed, perhaps due to the small patient cohort. In conclusion, we have identified NK cells and NK-like T-cells in the LN kidney and performed the first detailed analysis of their localization during active and inactive diseases. Their role in LN pathogenesis is, however, unclear and deserves further studies. We perform the first characterization of number and distribution of NK cells and NK like T cells in renal tissue in the active phase of LN disease and following immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Primary cutaneous lymphoma is a heterogeneous group of diseases where the malignant lymphocytes are primarily present in the skin at the time of diagnosis. The most common type of primary cutaneous lymphoma is mycosis fungoides. Early stages of mycosis fungoides present with flat or slightly elevated red skin lesions and can resemble eczema or psoriasis. In advanced stages erythrodermia or skin tumors can develop. For many patients with mycosis fungoides effective albeit not curative treatment is available. Large randomized treatment studies for mycosis fungoides are largely lacking, which makes decisions on treatment strategy difficult. The new national clinical guidelines will hopefully enable more equal care for patients with mycosis fungoides and other types of primary cutaneous lymphoma in Sweden.

The protein nucleobindin-2 (NUCB2, also known as nesfatin) was recently implicated as a mediator of anorexia and catabolism in the central nervous system, and has been suggested to act as a cleaved and secreted messenger. Given the overlap of signalling molecules between the brain and pancreas, we have explored the presence of NUCB2 in the islets of Langerhans. We also performed an investigation of the dynamic regulation of pancreatic NUCB2 in different metabolic states. NUCB2-like immunoreactivity was detected by immunofluorescence in all human and rat islet beta-cells (as detected by co-localization with insulin), but not in other islet cells or in the exocrine pancreas. Islet NUCB2 content, as measured by enzyme immunoassay, did not change significantly following an overnight fast, but was substantially lower in islets isolated from an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rats (48% of non-diabetic Wistar rat control). Serum levels, however, were not different between Wistar and GK rats. The release of NUCB2 from isolated rat islets was significantly elevated following glucose challenge (123%), but this effect was substantially lower than that observed for insulin (816%). In contrast, serum levels of NUCB2 showed a reversible decrease in an i.p. glucose tolerance test. These data suggest a role for NUCB2 in beta-cell function and a potential involvement in diabetic pathology. However, our findings, together with previous reports, appear more compatible with intracellular actions rather than with endocrine/paracrine communication, and suggest that NUCB2 in serum derives primarily from non-islet sources.

Prior to the development of type 1 diabetes, T cells are primed in the pancreatic lymph nodes (PLN) where they interact with APC displaying beta cell-derived peptides. The details concerning the regulation of autoreactive T cell responses in the PLN are unclear. BDC2.5/B6g7 TCR transgenic mice represent a simplified model of type 1 diabetes, in which beta cell-specific CD4+ T cells expressing a diabetogenic transgenic TCR are first activated in the PLN and subsequently home to the pancreas where they mediate killing of beta cells. DNAX-activating protein of 12 kDa (DAP12) is an adaptor molecule carrying an ITAM motif. It associates with receptors on lymphoid and myeloid cells, including APC. We here show that introduction of a DAP12 null mutation in BDC2.5/B6g7 mice accelerated diabetes development and promoted an augmented activation state of PLN T cells expressing the transgenic TCR. Transferred BDC2.5 T cells proliferated more efficiently in the PLN of DAP12-deficient B6g7 recipients, which correlated with a decreased impact of co-transferred BDC2.5+CD4+CD25+ T cells. We propose that signaling through a DAP12-associated receptor on APC facilitates activation of Treg in the PLN and by this contributes to the maintenance of peripheral tolerance to beta cell-derived antigens.