Somatostatin and substance P analogues: applications in autoimmune and haematological diseases

Somatostatin has been extensively studied in relation to the endocrine and nervous systems. Many reports on the role of somatostatin receptor imaging and somatostatin treatment of neuroendocrine tumours have been published. The relation between somatostatin and other neuropeptides and the immune system is less explored. The aim of this study was to investigate the diagnostic applications of somatostatin and substance P analogues in autoimmune and haematological diseases. Both in vivo and in vitro studies were performed, using peptide receptor scintigraphy in patients and rats, peptide receptor autoradiography on tissue biopsies, ligand binding assays on cell homogenates, and polymerase chain reactions on lymphoid cell lines. Moreover, based on the results of these studies, speculations were made about the therapeutical applications of somatostatin and substance P analogues in autoimmune and haematological diseases

Do synovial biopsies help to support evidence for involvement of innate immunity in the immunopathology of Behçet's disease?

Behçet's disease is a complex vasculitis of unknown etiology. Abundant neutrophils suggest the involvement of innate immunity. Cytokines are skewed to the T-helper-1 pattern. Few sterile organs are easily accessible for analysis in Behçet's disease. Cañete and coworkers identify inflamed joints as a feasible model and suggest the involvement of innate immunity in Behçet's disease

Reviewing primary Sjögren’s syndrome: Beyond the dryness - From pathophysiology to diagnosis and treatment

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This process leads to sicca syndrome, which is the combination of dryness of the eyes, oral cavity, pharynx, larynx and/or vagina. Extraglandular manifestations may also be prevalent in patients with pSS, including cutaneous, musculoskeletal, pulmonary, renal, hematological and neurological involvement. The pathogenesis of pSS is currently not well understood, but increased activation of B cells followed by immune complex formation and autoantibody production are thought to play important roles. pSS is diagnosed using the American-European consensus group (AECG) classification criteria which include subjective symptoms and objective tests such as histopathology and serology. The treatment of pSS warrants an organ based approach,

Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system

Cells of the human immune system have been shown to express somatostatin receptors (sst). The expression of sst suggests a functional role of the peptide somatostatin (SS). However, SS expression has not been demonstrated yet in different human immune tissues. Therefore, we investigated by RT-PCR the expression of both SS and cortistatin (CST), a SS-like peptide, in various human lymphoid tissues and immune cells. We detected SS mRNA expression in the human thymus only, while not in thymocytes. CST mRNA was clearly expressed in the immune cells, lymphoid tissues, and bone marrow. Using quantitative RT-PCR, significant differences in expression levels between tissues were demonstrated. Expression of CST mRNA was up-regulated during differentiation of monocytes into macrophages and dendritic cells and could be up-regulated by lipopolysaccharide stimulation. Two differently sized cDNA fragments of CST were detected in the majority of cells and tissues. However, although both fragments were detected in nearly all T-cell lines (7 of 8), most of the B-cell lines expressed the short fragment only (8 of 10). Usin

An inflammatory condition with different faces: Immunoglobulin G4-Related disease

__Background:__ Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition with involvement of different organs. The pathophysiological mechanism is unclear, but fibrosis is the hallmark of this disease. Early recognition is critical to avoid irreversible organ damage. Recently improved histological testing boosts the diagnostic yield. We present three cases of patients with IgG4-RD to emphasise the broad clinical presentation of this disease. __Case descriptions:__ Patient A, a 63-year-old male with bilateral orbital swelling due to IgG4-RD, was shown to suffer from IgG4-RD in a multifocal pattern as demonstrated by PET scanning. Patient B, a 53-year-old male with a long-standing abdominal mass of unknown origin, eventually proved to have IgG4-RD. Patient C was a 32-year-old male admitted with pleural effusion and pericardial tamponade. Histological diagnosis after pericardiectomy confirmed IgG4-RD. __Discussion:__ IgG4-RD has many faces and may mimic other conditions, such as malignancy and infectious diseases. Knowledge of this disease is needed to avoid unnecessary diagnostics and delay in treatment. IgG4-RD may be suspected based on specific clinical findings such as elevated serum IgG4 levels, but the diagnosis can only be established histologically. Although corticosteroids are an effective first choice of therapy, the relapse rate after this treatment remains high. The role of disease-modifying antirheumatic drugs in the treatment of IgG4-RD has not been outlined yet, but there is increasing evidence that rituximab might be an effective second-line therapy. __Conclusion:__ IgG4-RD is a disease with many faces requiring early recognition and therapy to avoid permanent damage of the organs

The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency

Background: Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case reports, recurrent infections and impaired immune cell function compatible with immunodeficiency were described. However, Jacobsen syndrome has not been recognized as an established syndromic primary immunodeficiency. Goal: To evaluate the presence of immunodeficiency in a series of 6 patients with JS. Methods: Medical history of 6 patients with JS was evaluated for recurrent infections. IgG, IgA, IgM and specific antibodies against S. pneumoniae were measured. Response to immunization with a polysaccharide vaccine (Pneumovax) was measured and B and T lymphocyte subset analyses were performed using flowcytometry. Results: Five out of 6 patients suffered from recurrent infections. These patients had low IgG levels and impaired response to S. pneumoniae polysaccharide vaccination. Moreover, we also found a significant decrease in the absolute number of memory B cells, suggesting a defective germinal center function. In a number of patients, low numbers of T lymphocytes and NK cells were found. Conclusions: Most patients with JS suffer from combined immunodeficiency in the presence of recurrent infections. Therefore, we consider JS a syndromic primary immunodeficiency. Early detection of immunodeficiency may reduce the frequency and severity of infections. All JS patients should therefore undergo immunological evaluation. Future studies in a larger cohort of patients will more precisely define the pathophysiology of the immunodeficiency in JS

Routine abdominal ultrasonography has limited value in the care for patients with indolent systemic mastocytosis

Objectives: Systemic mastocytosis (SM) is a myeloproliferative disease characterized by the accumulation of aberrant mast cells. Since advanced subtypes of SM can lead to organ dysfunction and shortened survival, timely recognition of progressive disease is important for the adequate treatment of SM patients. Methods: Here, we report the results of our cohort study on the value of routine abdominal ultrasonography for the detection of progression of indolent systemic mastocytosis (ISM). Results: We included 88 patients with ISM, of whom 9 developed new hepatosplenomegaly during follow-up. In this group, the median serum tryptase level increased by 11.60 μg/l, compared with a decrease of −0.20 μg/l in the 79 patients with unchanged ultrasonography results (p = 0.016). A change in liver and/or spleen size never led to a change in clinical classification, nor management. Discussion: Based on the finding that a change in ultrasonography findings did not correlate to disease progression in general, it appears that isolated hepatosplenomegaly does not have prognostic implications in patients with ISM. Conclusions: Routine abdominal ultrasonography is redundant in the follow-up of patients with ISM. A combination of physical examination with serum tryptase levels can be used to screen for hepatosplenomegaly