[Show abstract][Hide abstract] ABSTRACT: BackgroundA diagnosis of idiopathic anaphylaxis following a detailed clinical assessment remains very challenging for patients and clinicians. Risk reduction strategies such as allergen avoidance are not possible.Objective
This study investigated whether the (ISAC) allergy array with 103 allergens would add diagnostic value in patients with idiopathic anaphylaxis.Methods
We extended the specific IgE testing in 110 patients with a diagnosis of idiopathic anaphylaxis from five UK specialist centres using ISAC arrays. These were divided into three groups: Score I identified no new allergen sensitisation beyond those known by previous assessment. Score II identified new sensitisations which were not thought likely to explain the anaphylaxis and Score III identified new sensitisations felt to have a high likelihood of being responsible for the anaphylaxis. A proportion (50%) of Score III patients underwent clinical reassessment to substantiate the link to anaphylaxis in this group.ResultsThe results show that 20% of the arrays were classified as Score III with a high likelihood of identifying the cause of the anaphylaxis. A wide range of major allergens were identified, the most frequent being omega-5-gliadin and shrimp, together accounting for 45% of the previously unrecognised sensitisations.Conclusion
The ISAC array contributed to the diagnosis in 20% of patients with idiopathic anaphylaxis. It may offer additional information where a careful allergy history and follow on testing have not revealed the cause of the anaphylaxis.
[Show abstract][Hide abstract] ABSTRACT: Severe asymmetrical hypertrophic cardiomyopathy without heart block accompanied by neuromuscular hypotonia and feeding difficulties was evident shortly after birth in the second child of a mother with systemic lupus erythematosus who had no indication of gestational diabetes. High-level anti-ribonucleoprotein (RNP) and Smoth (Sm) antibodies arising from transplacental transfer of maternal antibodies were detected in the child's serum. The cardiac abnormalities improved with a commensurate decline in antibody titers. Previously reported cases of neonatal cardiomyopathy with endocardial fibroelastosis have been ascribed to the transplacental transfer of maternal Sjogrens Syndrome (SS) A (Ro) and Sjogrens Syndrome (SS) B (La) antibodies and have been more severe and persistent compared with our patient. We advocate close monitoring of all babies of mothers with systemic autoimmunity for changes in heart rate during pregnancy and signs of heart failure and neuromuscular weakness after delivery.
[Show abstract][Hide abstract] ABSTRACT: Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by disabling fatigue, headaches, sleep disturbance and several other symptoms. The onset of CFS may follow a viral infection or period of stress. Patients with CFS do not have hypogammaglobulinaemia, predisposition to recurrent bacterial infections or symptoms of autoimmunity. To date, defects in B cell numbers or function have not been shown in the literature. However, treatment with anti-B cell therapy using Rituximab has recently shown benefit to CFS patients. We therefore postulated that patients with CFS had a subtle humoral immune dysfunction, and performed extended B cell immunophenotyping. We undertook a detailed characterization of the proportions of the different B cell subsets in 33 patients with CFS fulfilling the Canadian and Fukada criteria for CFS and compared these with 24 age- and gender-matched healthy controls (HC). CFS patients had greater numbers of naive B cells as a percentage of lymphocytes: 6·3 versus 3·9% in HC (P = 0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P = 0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P = 0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P = 0·013). While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.
[Show abstract][Hide abstract] ABSTRACT: Granulomas that occur in sarcoidosis are histologically identical to those found in a subset of Common Variable Immunodeficiency (CVID) patients where they are associated with a reduction in class switched memory B lymphocytes. The aim of this study was to investigate whether the abnormalities in peripheral blood lymphocyte populations associated with granulomatous variant CVID (gvCVID) are also present in individuals with sarcoidosis. We examined B lymphocyte populations using flow cytometry and found that the reduction of class switched memory (CSM: CD19+CD27+IgM-IgD-) and unswitched memory (CD19+CD27+IgM+IgD+) B cells in our sarcoidosis cohort was similar to that previously reported in gvCVID patients. The reduction of class switched memory B cells in sarcoidosis patients indicated a possible defect in the T cell repertoire as antibody class switching requires T cell help. We subsequently explored the peripheral blood T cell compartment of our sarcoidosis patients. The results identified a population of terminally differentiated effector CD8+ T cells (CCR7-CD45RA-CD127-CD27-CD28-) that were significantly expanded in the peripheral blood of sarcoidosis patients. Terminally differentiated effector CD8+ T cells have been defined as cytolytic, inflammatory cells with reduced replicative capacity. The discovery of abnormal peripheral blood B and T cells compartments in sarcoidosis may be of value in clinical diagnosis and could be relevant to the pathogenic process.
Journal of Clinical and Cellular Immunology. 12/2012; 3(4):132.
[Show abstract][Hide abstract] ABSTRACT: The chronic fatigue syndrome (CFS), as defined by recent criteria, is a heterogeneous disorder with a common set of symptoms that often either follows a viral infection or a period of stress. Despite many years of intense investigation there is little consensus on the presence, nature and degree of immune dysfunction in this condition. However, slightly increased parameters of inflammation and pro-inflammatory cytokines such as interleukin (IL) 1, IL6 and tumour necrosis factor (TNF) α are likely present. Additionally, impaired natural killer cell function appears evident. Alterations in T cell numbers have been described by some and not others. While the prevalence of positive serology for the common herpes viruses appears no different from healthy controls, there is some evidence of viral persistence and inadequate containment of viral replication. The ability of certain herpes viruses to impair the development of T cell memory may explain this viral persistence and the continuation of symptoms. New therapies based on this understanding are more likely to produce benefit than current methods.
Brain Behavior and Immunity 07/2011; 26(1):24-31. · 5.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recurrent episodic fever of unknown origin (FUO) arising from tumour of the gastrointestinal tract is rare. We report an otherwise healthy 62-year-old man with recurrent circumscribed bouts of fever and raised CRP for 3 years who has remained well and fever-free 2 years after the removal of a well-differentiated adenocarcinoma of the colon. Occult colonic neoplasm should be considered and sought when routine investigations for FUO are negative.
Case reports in infectious diseases. 01/2011; 2011:271808.
[Show abstract][Hide abstract] ABSTRACT: Chronic idiopathic urticaria (CIU) is well known to be associated with antithyroid peroxidase antibodies and autoimmune thyroiditis. Coexisting Graves disease has only rarely been observed. We describe 2 patients with CIU who developed autoimmune hyperthyroidism with antithyrotropin receptor antibodies. Antithyroid peroxidase antibodies were also present in 1 of the patients, but both responded poorly to high-dose antihistamine therapy. Both patients improved significantly, and their thyroid function recovered with carbimazole. We advise clinicians to be alert to the symptoms of hyperthyroidism when patients with CIU respond poorly to antihistamine therapy, as prompt treatment of hyperthyroidism significantly improves urticaria.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2009; 19(1):54-6. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of prednisolone on NK cell cytotoxicity in vitro environment and also to compare the effect of prednisolone versus immunoglobulin-G (IVIG) on NK cell cytotoxicity using in vitro co-culture with K562 cells.
The following is a prospective observational study, between August 2006 and February 2007, was carried out on blood samples from 110 patients with a history of recurrent miscarriage or recurrent failed implantation. Peripheral blood mononuclear cells containing NK cells were isolated and co-cultured with target cell K562 in three different effector-to-target (E:T) ratios of 50:1, 25:1 and 12.5:1. Prednisolone or IVIG was then added to the tube with E:T ratio of 50:1 to assess suppressive effect. The percentage killing was recorded and statistical analysis performed using Student's t-test.
In the experiments with an E:T ratio of 50:1 without prednisolone or IVIG in the co-culture, the mean target cell killing percentage was 26.4%. In cultures using the same E:T ratio, this killing percentage was significantly reduced in the presence of IVIG (9.9%) or prednisolone (13.6%), (P<0.001 in both analyses). On comparing the reduction in killing percentage of target cells by prednisolone versus IVIG, a slightly lower reduction in the prednisolone co-culture was noted but this was not statistically significant (P>0.05).
The results of this study show that prednisolone is able to suppress the cytolytic activity of the NK cell. Prednisolone and IVIG are almost equally effective in suppressing in vitro NK cell cytolytic activity.
American journal of reproductive immunology (New York, N.Y.: 1989) 03/2008; 59(3):259-65. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis.
Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls.
Peritoneal fluid levels of MCP-1, IL-8 and IL-6 were significantly higher in the endometriosis group (P < 0.012, P = 0.003, and P = 0.015, respectively). There was no significant difference in the peritoneal fluid levels of IL-1 beta, TNF-alpha, RANTES, VEGF, PDGF, sFas and sFasL in the two groups. Although serum levels of IL-8 were higher in women with endometriosis, the difference was not significant (P = 0.07). Serum levels of PDGF, IL-6, RANTES, IL-1 beta, TNF-alpha, and sFas, were not significantly different in the two groups.
The elevated levels of MCP-1, IL-6, and IL-8 in peritoneal fluid but not serum may indicate the importance of local macrophage activating factors in the pathogenesis of endometriosis.
Journal of Obstetrics and Gynaecology Research 09/2007; 33(4):490-5. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the association of serum tumour necrotic factor (TNF)-alpha and interferon (IFN)-gamma levels with IVF treatment outcome and peripheral blood NK cells.
Prospective observational study of 126 randomly selected women who underwent IVF treatment. The serum levels of TNF-alpha and IFN-gamma were determined by multiplex suspension beads array system.
There were no significant differences with regard to the systemic TNF-alpha and IFN-gamma levels between the pregnant (n = 51, TNF-alpha: 53.5 pg/mL; IFN-gamma: 4.6 pg/mL) and not pregnant (n = 75, TNF-alpha: 63.0; IFN-gamma: 7.5) women after IVF treatment. For those women with a positive pregnancy after IVF treatment, the systemic TNF-alpha and IFN-gamma levels were higher in those women who miscarried (n = 13, TNF-alpha: 67.4; IFN-gamma: 9.1) when compared with those who had a live birth (n = 38, TNF-alpha: 48.7; IFN-gamma: 1.4), however this difference was not statistically significant. Interestingly, the systemic TNF-alpha and IFN-gamma levels were significantly higher in women who had a higher level of activated (CD69(+)) NK cells (n = 39, TNF-alpha: 86.8; IFN-gamma: 4.7) when compared with women who had a low level of activated NK cells (n = 87, TNF-alpha: 46.9; IFN-gamma: 1.7 P = 0.028 and 0.045 respectively).
The systemic levels of TNF-alpha and IFN-gamma have no association with implantation rate or miscarriage rate in women undergoing IVF treatment. However, high levels of TNF-alpha and IFN-gamma are associated with elevated levels of activated NK cells and this may subsequently exert a negative impact on reproduction.
American journal of reproductive immunology (New York, N.Y.: 1989) 04/2007; 57(3):210-7. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brazil nuts are the second most frequent cause of nut allergy in the United Kingdom. We report the case of a 20-year-old woman with documented Brazil nut allergy who developed widespread urticaria and mild dyspnea after intercourse with her boyfriend who had earlier consumed Brazil nuts. Skin prick testing with the boyfriend's semen after Brazil nut consumption confirmed significant reactivity whereas a sample before nut consumption was negative. We believe this to be the first case of a sexually transmitted allergic reaction.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2007; 17(3):189-91. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the association between the absolute counts of the peripheral natural killer (NK) cells (including total CD56(+) NK cells, CD56(dim) NK cells and CD56(bright) NK cells), B cells and T cells on the implantation rate and miscarriage rate after IVF treatment.
This was a prospective observation study. A total of 138 patients who underwent IVF treatment from December 2002 to July 2003 were recruited to the study. Blood samples were obtained on the day of vaginal oocyte retrieval prior to the procedure. The absolute counts of lymphocytes, NK cells, B cells and T cells were identified by flow cytometry. These absolute counts and their relationships to IVF treatment outcome and miscarriage rate were analysed.
There were no significant differences with regard the mean values of absolute lymphocyte count, T cell count, B cell count and NK cell count (including total CD56(+) NK, CD56(dim) NK and CD56(bright) NK cells) between the pregnant and non-pregnant groups and also between the ongoing pregnancy and miscarriage groups. The cause of infertility, duration of infertility, basal FSH levels, number of previous failed IVF treatments, number of previous miscarriages and stimulation characteristics were not significantly different between the pregnant and non-pregnant groups. Previous studies have suggested that women with a history of recurrent miscarriage and those with infertility accompanied by recurrent failed IVF treatments are associated with a peripheral blood NK cell percentage >12%, therefore further analysis of peripheral CD56(+) NK cell levels <12% (group A) and >12% (group B) was performed. There was no significant difference in implantation rate (group A: 17.0%; group B: 23.2%), pregnancy rate (group A: 36.6%; group B: 47.7%) or miscarriage rate (group A: 23.3%; group B: 28.6%).
There were no significant differences between simple enumerations of peripheral blood NK cells (including total CD56(+) NK, CD56(dim) NK and CD56(bright) NK cells), B cells and T cells with IVF treatment outcome and pregnancy outcome. Women who had a peripheral NK cell level >12% did not have higher number of previous pregnancy losses. Importantly their pregnancy rate was not reduced and their miscarriages were not increased compared to women who had a peripheral NK cells level <12%.
Human Reproduction 06/2005; 20(5):1272-6. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Graft-versus-host disease (GvHD) complicates many allogeneic stem cell transplants (alloSCT), and several factors are known to be associated with the development of GvHD besides human leucocyte antigen (HLA) incompatibility. We investigated whether changes in serum levels of soluble IL-2 receptor (sIL-2Ralpha), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF) and soluble Fas (sFas) correlated with the development of GvHD in patients undergoing SCT, and might thus be potentially of use to anticipate the development of GvHD, allowing early modification of immunosuppressive therapy.sIL2Ralpha and sFas levels were significantly raised in allograft, autograft (allo and auto) and non-graft groups compared to the normal controls (HC), but there was no statistical difference between the three patient groups. TNF-alpha was raised in the auto and allo groups and the non-graft patients compared to the HC group (median 4.37 pg/ml), but only reached significance in the allo group (median 6.02 pg/ml; p = 0.008) when this was compared with the non-graft patients. There was no significant difference in TGF-ss levels between any of the groups. The median serum VEGF levels were decreased in allo and auto patients compared to HC, (31 and 62 pg/ml versus 90 pg/ml, respectively), with a significant difference in the auto group (p = 0.007). VEGF levels were significantly lower in the auto versus the allo group (p = 0.008) and also in the auto versus the non-graft group (median 104 pg/ml; p = 0.011). When the allo group was divided into patients who developed GvHD and those who did not, serum VEGF levels were significantly higher in those with GvHD (p = 0.028).
[Show abstract][Hide abstract] ABSTRACT: Our aim was to evaluate the effect of the absolute count of the activation marker (CD69), IgG Fc receptor (CD16) and inhibitor marker (CD94) expression on peripheral blood natural killer (NK) cells on implantation and miscarriage rates after IVF treatment.
Prospective observational study of 138 randomly selected women who underwent IVF treatment from December 2002 to September 2003. NK cells were identified as CD56(+) (dim + bright) and CD3(-) by flow cytometry. The absolute counts of the CD69(+), CD16(+) and CD94(+)expressing NK cells were recorded and their relation to IVF treatment outcome and miscarriage rate was analysed.
The mean (+/-SD) absolute count of the CD56(dim)CD16(+)CD69(+) NK cells for women who had a successful ongoing pregnancy was 0.61 x 10(6)/l (+/-0.31). For those women who failed to achieve a pregnancy, the mean value of the absolute count of CD56(dim)CD16(+)D69(+) NK cells was significantly (P=0.003) higher at 1.66 x 10(6)/l (+/-0.52). The absolute count of CD56(dim)CD16(+)CD94(+) and CD56(dim)CD16(+) NK cells did not show any statistically significant differences between those women with successful and failed IVF treatment. Receiver operating characteristic (ROC) curve analysis was performed to select a CD69 threshold for further statistical analysis. The implantation rate (IR) was significantly lower (13.1%) and miscarriage rate (MR) was significantly higher (66.7%) for women with an absolute CD56(dim)CD16(+)CD69(+) NK cell count of >1.0 x 10(6)/l compared to women with count below this value (IR 28.2% and MR 16.7%). Further analysis of the absolute count of CD56(bright)CD69(+) and CD56(bright)CD94(+) NK cells did not show any significant difference between those women with successful and failed IVF treatment.
An increase in the absolute count of activated NK cells (CD56(dim)CD16(+)CD69(+)) in the peripheral blood is associated with a reduced rate of embryo implantation in IVF treatment. Furthermore, women with high CD56(dim)CD16(+)CD69(+) peripheral blood NK cell absolute count, who are able to achieve pregnancy, have a significantly higher miscarriage rate.
Human Reproduction 10/2004; 19(10):2395-400. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether serum vascular endothelial growth factor (VEGF) levels can distinguish highly responsive women who subsequently develop ovarian hyperstimulation syndrome (OHSS) from women with a similar ovarian response who do not.
Prospective controlled study.
University IVF unit.
Women undergoing IVF who met predetermined risk criteria for OHSS. Patients developing OHSS were compared with patients who did not develop OHSS.
Long-protocol pituitary down-regulation followed by FSH stimulation by a standard protocol without coasting. A maximum of three embryos was transferred. Vaginal progesterone was used for luteal support.
Occurrence of OHSS; serum VEGF concentrations on the day of embryo transfer (ET) and at 5 and 10 days after ET.
Serum VEGF levels at any time point did not differ significantly between 9 OHSS cases and 9 controls. Vascular endothelial growth factor levels in samples collected from cases before the onset of OHSS were higher than levels in time-matched samples from controls (medians, 177.6 [range, 64.02-549.1] pg/mL vs. 100.7 [range, 37.59-246] pg/mL, respectively), but the difference failed to reach statistical significance (P=.0518), and there was considerable overlap between cases and controls.
Serum VEGF levels in the luteal phase do not distinguish between high-risk women who subsequently develop OHSS and women with a similar risk profile who do not develop OHSS.
Fertility and Sterility 01/2003; 78(6):1154-8. · 4.17 Impact Factor