Dw/LD-related molecular polymorphism of DR4 β-chains

The results of this study demonstrate the existence of molecular heterogeneity (polymorphism) within DR β-chains isolated from a single serologically defined DR phenotype, DR4. The data are consistent with the possibility that this polymorphism is related to the Dw/LD phenotype as defined with the cellular reagents, homozygous typing cells.     

Myeloid‐derived suppressor cells increase and inhibit donor‐reactive T cell responses to graft intestinal epithelium in intestinal transplant patients

Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal and multivisceral transplant (ITx) recipient survival. We investigated the role of myeloid‐derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33⁺CD11b⁺ lineage(CD3/CD56/CD19)^?HLA‐DR^?/low cells with 3 subsets, CD14^?CD15^? (e‐MDSCs), CD14⁺CD15^? (M‐MDSCs), and CD14^?CD15⁺ (PMN‐MDSCs), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs after ITx; among MDSC subsets, M‐MDSC numbers were maintained at a high level after 2 months post ITx. The MDSC numbers decreased in ITx recipients with ACR. MDSC numbers were positively correlated with serum interleukin (IL)‐6 levels and the glucocorticoid administration index. IL‐6 and methylprednisolone enhanced the differentiation of bone marrow cells to MDSCs in vitro. M‐MDSCs and e‐MDSCs expressed CCR1, ‐2, and ‐3; e‐MDSCs and PMN‐MDSCs expressed CXCR2; and intestinal grafts expressed the corresponding chemokine ligands after ITx. Of note, the percentage of MDSCs among intestinal mucosal CD45⁺ cells increased after ITx. A novel in vitro assay demonstrated that MDSCs suppressed donor‐reactive T cell–mediated destruction of donor intestinal epithelial organoids. Taken together, our results suggest that MDSCs accumulate in the recipient PBMCs and the grafted intestinal mucosa in ITx, and may regulate ACR.     

Activation of the contact system in insect-sting anaphylaxis: association with the development of angioedema and shock

A postulated role of the contact system in anaphylactic reactions to insect stings was investigated. During prospective, in-hospital sting challenge, we collected serial blood samples from five normal volunteers and 16 patients with a history of insect-sting anaphylaxis. Activation of the contact system was assessed by measuring plasma levels of factor XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes as well as those of cleaved high molecular weight kininogen (HK). In addition, antigenic levels of (pre)kallikrein, factor XII, and HK were measured. No significant changes in contact system parameters were observed in any of the five volunteers or the four patients who did not develop an anaphylactic reaction after sting challenge. In contrast, significant changes in contact system parameters occurred in 7 of the 12 patients with anaphylactic symptoms after challenge. Peak levels of either C1-inhibitor complex were found 5 minutes after the onset of anaphylactic symptoms. The increase in C1-inhibitor was most pronounced in the 4 patients with angioedema, 2 of which also developed shock. However, activation of HK was observed in all four patients with angioedema, the two patients with shock but no angioedema, as well as in 1 of the remaining 6 patients with anaphylactic symptoms other than angioedema or shock. Thus, activation products of the contact system may be involved in the pathogenesis of angioedema and shock in insect- sting anaphylaxis.     

Patients who develop inflammatory polyarthritis (IP) after immunization are clinically indistinguishable from other patients with IP

Musculoskeletal symptoms may occur following various types of immunization, and it has also been suggested that, like infection, immunization may act as a trigger for rheumatoid arthritis (RA). A total of 48 of 898 (5.3%) patients with early inflammatory polyarthritis (IP) referred to the Norfolk Arthritis Register reported an immunization in the 6 weeks prior to symptom onset. There were no important clinical or demographic differences between the 48 immunized patients and 185 consecutive patients who did not report prior immunization. In addition, the frequencies of HLA-DRB1*01. *04 and the shared epitope in 33 of the immunized patients were similar to those in the 185 non-immunized patients and to those in 136 healthy controls. Further results from a case-control study suggest that the rate of immunization is higher amongst cases (5.5%) than age- and sex-matched controls (2.8%). In a small number of susceptible individuals, immunization may thus act as a trigger for RA.      

Images in geriatric cardiology. Usefulness of live three-dimensional transthoracic echocardiography in aortic valve stenosis evaluation

Aortic valve stenosis (AS) severity can be estimated by various modalities. Due to some of the limitations of the currently available methods, the usefulness of live three-dimensional transthoracic echocardiography (3D TTE) in the assessment of AS was explored. Live 3D TTE was able to visualize the aortic valve orifice in all 11 patients studied. Live 3D TTE correctly estimated the severity of AS in all 10 patients in whom AS severity could be evaluated at surgery. These included eight patients with severe AS and two with moderate AS. Two of these 10 patients with AS had associated hypertrophic cardiomyopathy and underwent myectomy at the time of aortic valve replacement. Aortic valve orifice area measurements by live 3D TTE correlated well with intraoperative three-dimensional transesophageal echocardiographic reconstruction measurements (r=0.85) but not as well with two-dimensional transesophageal echocardiography measurements (r=0.64). Live 3D TTE measurements of the aortic valve orifice area also did not correlate well with two-dimensional transthoracic echocardiography measurements (r=0.46) but the number of patients studied with two-dimensional transthoracic echocardiography was smaller (only seven) and four of these did not undergo two-dimensional transthoracic echocardiography at the authors' institution. Altogether, four patients with severe AS by live 3D TTE, and subsequently confirmed at surgery, were misdiagnosed as having moderate AS by two-dimensional transthoracic echocardiography. Because it is completely noninvasive and views the aortic valve in three dimensions, 3D TTE could be a useful complement to the existing modalities in the evaluation of AS severity.     

Respiratory syncytial virus infection in patients with hematological diseases: single-center study and review of the literature.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant mortality in patients with hematological diseases, but diagnosis and treatment are uncertain. METHODS: We retrospectively identified RSV-infected patients with upper or lower respiratory tract infection (RTI) by culture, antigen testing, and polymerase chain reaction from November 2002 through April 2007. Patients with severe immunodeficiency (SID; defined as transplantation in the previous 6 months, T or B cell depletion in the previous 3 months, graft-versus-host disease [grade, >or=2], leukopenia, lymphopenia, or hypogammaglobulinemia) preferentially received oral ribavirin, intravenous immunoglobulin, and palivizumab. The remaining patients with moderate immunodeficiency (MID) preferentially received ribavirin and intravenous immunoglobulin. RESULTS: We identified 34 patients, 22 of whom had upper RTI (10 patients with MID and 12 with SID) and 12 of whom had lower RTI (2 with MID and 10 with SID). Thirty-one patients were tested by polymerase chain reaction (100% of these patients had positive results; median RSV load, 5.46 log(10) copies/mL), 30 were tested by culture (57% had positive results), and 25 were tested by antigen testing (40% had positive results). RSV-attributed mortality was 18% (6 patients died) and was associated with having >or=2 SID factors (P=.04), lower RTI (P=.01), and preengraftment (P=.012). Among 12 patients with MID (7 of whom received treatment), no progression or death occurred. Nine patients with SID and upper RTI received treatment (7 patients received ribavirin, intravenous immunoglobulin, and palivizumab); infection progressed to the lower respiratory tract in 2 patients, and 1 patient died. Ten patients with SID and lower RTI were treated, 5 of whom died, including 4 of 6 patients who received ribavirin, intravenous immunoglobulin, and palivizumab. The duration of RSV shedding correlated with the duration of symptoms in patients with SID but exceeded symptom duration in patients with MID (P<.05). CONCLUSIONS: Lower RTI, >or=2 SID criteria, and preengraftment are risk factors for RSV-attributed mortality. Polymerase chain reaction may optimize diagnosis and monitoring. Oral ribavirin therapy seems safe, but trials are needed to demonstrate its efficacy.     

Multinational Qualitative Research Study Exploring the Patient Experience of Raynaud's Phenomenon in Systemic Sclerosis

Objective

Raynaud's phenomenon (RP) is the most common manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self‐report. A thorough understanding of the patient experience of SSc‐RP is essential to ensuring that patient‐reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc‐RP.

Methods

Focus groups of SSc patients were conducted across 3 scleroderma centers in the US and UK, using a topic guide and a priori purposive sampling framework devised by qualitative researchers, SSc patients, and SSc experts. Focus groups were audio recorded, transcribed, anonymized, and analyzed using inductive thematic analysis. Focus groups were conducted until thematic saturation was achieved.

Results

Forty SSc patients participated in 6 focus groups conducted in Bath (UK), New Orleans (Louisiana), and Pittsburgh (Pennsylvania). Seven major themes were identified that encapsulate the patient experience of SSc‐RP: physical symptoms, emotional impact, triggers and exacerbating factors, constant vigilance and self‐management, impact on daily life, uncertainty, and adaptation. The interrelationship of the 7 constituent themes can be arranged within a conceptual map of SSc‐RP.

Conclusion

We have explored the patient experience of SSc‐RP in a diverse and representative SSc cohort and identified a complex interplay of experiences that result in significant impact. Work to develop a novel PRO instrument for assessing the severity and impact of SSc‐RP, comprising domains/items grounded in the patient experiences of SSc‐RP identified in this study, is underway.