Exacerbation of hypereosinophilic syndrome with pulmonary involvement in two consecutive pregnancies: a case report and review of the literature

Hypereosinophilic syndrome represents a heterogeneous group of disorders with the common feature of prolonged eosinophilia of unknown cause and organ system dysfunction including the pulmonary system. Hypereosinophilic syndrome, with and without pulmonary involvement, in association with pregnancy is very rare, and to the best of our knowledge only one case of hypereosinophilic syndrome with pulmonary involvement during pregnancy has been previously reported in the medical literature. We describe a case of a patient with previously symptomatic hypereosinophilic syndrome with pulmonary involvement who experienced exacerbations of her disease during two consecutive pregnancies. To the best of our knowledge this is the first report which demonstrates a worsening effect of pregnancy on both eosinophil count and end organ involvement in a patient with previous diagnosis of hypereosinophilic syndrome

Isolated periaortitis: Clinical and imaging characteristics

Chronic periaortitis includes a variety of conditions that have similar clinical and histopathological findings, and thus probably represents different manifestations of the same disease: idiopathic retroperitoneal fibrosis, perianeurysmal retroperitoneal fibrosis, and inflammatory abdominal aortic aneurysms. We describe the clinical and imaging characteristics of the nonaneurysmal form of chronic periaortitis, recognized as isolated periaortitis, in an adult male patient presented with low back pain

Chronic Stanford type A aortic dissection manifesting as systemic inflammatory disorder

Typical presentation of type A aortic dissection usually encompasses severe acute chest pain, frequently radiating to the upper back, which is seen in more than 80% of the patients, while isolated back or abdominal pain have been repeatedly reported as the first manifestation of the disease as well. Occasionally, dyspnea due to acute aortic regurgitation, syncope, or stroke, secondary to obstruction of major cerebral vessels, have also been described at presentation of type A aortic dissection. Presentation of aortic dissection as a prolonged systemic illness with a number of nonspecific clinical and laboratory findings, such as low-grade fever, fatigue, malaise, weight loss, anemia, elevated acute phase response laboratory parameters, and absence of any of typical clinical features of the dissection syndrome has been only rarely reported. We describe a patient with type A chronic aortic dissection, manifesting as a systemic inflammatory disorder in the absence of acute chest syndrome. The diagnosis was made accidentally by computed tomography, ordered in the course of the regular work up. The patient underwent emergent surgery with resection and grafting of the dissected aorta. Pathological investigation demonstrated intense acute inflammation with neutrophilic infiltration in the vicinity of the intramural hemorrhage and necrosis, as well as granulation tissue with new vessels formation and collagen deposition in the outer media. The possible pathogenic mechanisms of the phenomenon are discussed

Soluble CD147 regulates endostatin via its effects on the activities of MMP-9 and secreted proteasome 20S

During progression of rheumatoid arthritis (RA), angiogenesis provides oxygen and nutrients for the cells’ increased metabolic demands and number. To turn on angiogenesis, pro-angiogenic factors must outweigh anti-angiogenic factors. We have previously shown that CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) can induce the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9) in a co-culture of the human HT1080 fibrosarcoma and U937 monocytic-like cell lines. However, whether CD147 influences anti-angiogenic factors was not known. We now show that relative to single cultures, the co-culture of these cells not only enhanced pro-angiogenic factors but also decreased the anti-angiogenic factors endostatin and thrombospondin-1 (Tsp-1), generally increasing the angiogenic potential as measured by a wound assay. Using anti-CD147 antibody, CD147 small interfering RNA (siRNA), and recombinant CD147, we demonstrate that CD147 hormetically regulates the generation of endostatin but has no effect on Tsp-1. Since endostatin is cleaved from collagen XVIII (Col18A), we applied different protease inhibitors and established that MMP-9 and proteasome 20S, but not cathepsins, are responsible for endostatin generation. MMP-9 and proteasome 20S collaborate to synergistically enhance endostatin generation, and in a non-cellular system, CD147 enhanced MMP-9 activity and hormetically regulated proteasome 20S activity. Serum samples obtained from RA patients and healthy controls mostly corroborated these findings, indicating clinical relevance. Cumulatively, these findings suggest that secreted CD147 mediates a possibly allosteric effect on MMP-9 and proteasome 20S activities and can serve as a switch that turns angiogenesis on or off, depending on its ambient concentrations in the microenvironment

Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats

Spondyloarthritis (SpA) does not display the typical features of auto-immune disease. Despite the strong association with MHC class I, CD8+ T cells are not required for disease induction in the HLA-B27/Huβ2m transgenic rats. We used Lewis HLA-B27/Huβ2m transgenic rats [21-3 × 283-2]F1, HLA-B7/Huβ2m transgenic rats [120-4 × 283-2]F1, and wild-type rats to test our hypothesis that SpA may be primarily driven by the innate immune response. In vitro, splenocytes were stimulated with heat-inactivated Mycobacterium tuberculosis and cytokine expression and production was measured. In vivo, male and female rats were immunized with 30, 60, or 90 µg of heat-inactivated M. tuberculosis and clinically monitored for spondylitis and arthritis development. After validation of the model, we tested whether prophylactic and therapeutic TNF targeting affected spondylitis and arthritis. In vitro stimulation with heat-inactivated M. tuberculosis strongly induced gene expression of pro-inflammatory cytokines such as TNF, IL-6, IL-1α, and IL-1β, in the HLA-B27 transgenic rats compared with controls. In vivo immunization induced an increased spondylitis and arthritis incidence and an accelerated and synchronized onset of spondylitis and arthritis in HLA-B27 transgenic males and females. Moreover, immunization overcame the protective effect of orchiectomy. Prophylactic TNF targeting resulted in delayed spondylitis and arthritis development and reduced arthritis severity, whereas therapeutic TNF blockade did not affect spondylitis and arthritis severity. Collectively, these data indicate that innate immune activation plays a role in the initiation of HLA-B27-associated disease and allowed to establish a useful in vivo model to study the cellular and molecular mechanisms of disease initiation and progression

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Antiviral Treatment Down-Regulates Peripheral B-Cell CD81 Expression and CD5 Expansion in Chronic Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation. Recently, CD81 was identified as an HCV receptor on B lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. It has recently been shown that peripheral B-cell CD81 overexpression and CD5(+) subpopulation expansion correlate with HCV viral load and are associated with the development of HCV-related autoimmunity. In the present study, we assessed the effects of combination antiviral therapy (alfa interferon and ribavirin) on peripheral B-cell CD81 expression and CD5 expansion and the presence of autoimmune markers. Peripheral B-cell CD5 expression and the mean fluorescence intensity of CD81 were assessed by flow cytometry before and after treatment in 15 HCV-infected patients, in 10 untreated patients, and in 25 healthy controls. A significant posttreatment decrease in peripheral B-cell CD81 expression and disappearance of CD5(+) B-cell expansion were observed in all nine patients in whom a complete and sustained virological response was achieved (P < 0.01) (comparable to those for healthy controls). The decrease in CD81 overexpression and CD5 expansion in these patients was associated with a decrease and/or disappearance of autoimmune markers. In contrast, in nonresponders overexpression of CD81 and expansion of the CD5(+) B-cell subpopulation were not significantly changed and were comparable to those for untreated patients. In conclusion, antiviral therapy down-regulates peripheral B-cell CD81 expression and the CD5(+) population, either directly or by its effect on HCV RNA load. The overexpression of CD81 and the expansion of the population of CD5(+) peripheral B cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation

Chronic Stanford type A aortic dissection manifesting as systemic inflammatory disorder

Typical presentation of type A aortic dissection usually encompasses severe acute chest pain, frequently radiating to the upper back, which is seen in more than 80% of the patients, while isolated back or abdominal pain have been repeatedly reported as the first manifestation of the disease as well. Occasionally, dyspnea due to acute aortic regurgitation, syncope, or stroke, secondary to obstruction of major cerebral vessels, have also been described at presentation of type A aortic dissection. Presentation of aortic dissection as a prolonged systemic illness with a number of nonspecific clinical and laboratory findings, such as low-grade fever, fatigue, malaise, weight loss, anemia, elevated acute phase response laboratory parameters, and absence of any of typical clinical features of the dissection syndrome has been only rarely reported. We describe a patient with type A chronic aortic dissection, manifesting as a systemic inflammatory disorder in the absence of acute chest syndrome. The diagnosis was made accidentally by computed tomography, ordered in the course of the regular work up. The patient underwent emergent surgery with resection and grafting of the dissected aorta. Pathological investigation demonstrated intense acute inflammation with neutrophilic infiltration in the vicinity of the intramural hemorrhage and necrosis, as well as granulation tissue with new vessels formation and collagen deposition in the outer media. The possible pathogenic mechanisms of the phenomenon are discussed

The Expansion of CD25highIL-10highFoxP3high B Regulatory Cells Is in Association with SLE Disease Activity

B regulatory cells (Bregs) belong to a subgroup of activated B cells tasked with maintaining self-tolerance and preventing autoimmunity. While sharing similar regulatory mechanisms such as IL-10 dependency, they also defer in exhibiting their suppressive effects by expressing Fas-Ligand, TGF-beta, and PDL-1. In this study we show, for the first time, the expansion of CD25highFoxP3high Bregs in systemic lupus erythematosus (SLE) patients compared to healthy individuals (18.5 ± 3.052% versus 11.0 ± 1.654%, p<0.001, resp.). This expansion was also shown to correlate with SLE disease activity (r=0.75). In addition, CD25highFoxP3high Bregs were also IL-10high expressing and further expanded when stimulated with semaphorin 3A. In sum we show that CD25highFoxP3high are an additional subtype of Bregs, involved in regulating SLE disease activity. Being IL-10 expressing, we may assume that they are one of the sources of increased serum IL-10 in SLE patients. Further studies are required in order to assess the relation between high serum IL-10 and CD25highFoxP3high Breg cells