[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: OBJECTIVE: The aim of this case-control study at 30-33 weeks, a few days or weeks before the clinical onset of preeclampsia (PE), was to assess whether serum concentrations of cytokines differ between patients who are destined to develop PE and those with uncomplicated pregnancies. METHODS: A panel of cytokines was measured using Luminex technology at 30-33 weeks' gestation in 39 cases that developed PE at or after 34 weeks and 117 unaffected controls. RESULTS: The serum concentrations of most analysed cytokines were no different in women who developed PE than in controls. The proportion of women with detectable concentrations of MIP-1α and IL-8 were significantly lower in those with PE than in the controls (MIP-1α: 14/39 vs. 76/117, P = 0.003; IL-8:13/39 vs. 83/117, P < 0.0001). The median maternal serum concentration of IL-1β was significantly lower in the PE cases than in the controls (0.38 pg/mL, range 0.01-0.92, vs. 0.60 pg/mL, range 0.02-3.54, P = 0.005). CONCLUSION: Our findings do not lend support to the hypothesis that systemic inflammation precedes the onset of PE or that cytokines are good markers for such inflammation and certainly the panel of cytokines we examined does not provide useful prediction of subsequent development of PE. This article is protected by copyright. All rights reserved.
[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: Increased peripheral blood-activated NK cell counts are associated with increased risk of miscarriage and failed in vitro fertilization treatment. However, assessment of activated peripheral NK cells in normal and pathological pregnancies beyond implantation and early miscarriage has not been described. Total CD69 expressing NK cells counts were measured by flow cytometry in healthy women with singleton pregnancies, including 45 at 11+6–13+6 weeks’ gestation, 46 at 20+0–22+4 weeks, and 42 at 31+6–33+5 weeks. The number of peripheral blood NK cells decreased, whereas the percentage of activated CD69 expressing NK cells increased from the first to the third trimester of pregnancy. This study shows the course of peripheral blood NK cells and activated CD69 expressing NK cells in uncomplicated nulliparous singleton pregnancies. This is a first step in understanding their implication in pathological pregnancies.
International Journal of Reproductive Medicine. 03/2013; 2013.
[show abstract][hide abstract] ABSTRACT: Human chorionic gonadotrophin (hCG) is released within hours of fertilization and has a profound ability to downregulate maternal cellular immunity against trophoblastic paternal antigens. It also promotes angiogenic activity of the extravillous trophoblast, and impairment of this function may lead to inadequate placentation and an increased risk of preeclampsia. There is increasing evidence that hCG alters the activity of dendritic cells via an upregulation of indoleamine 2,3-dioxygenase activity. This reduces T-cell activation and cytokine production, as well as encouraging Treg cell recruitment to the fetal-maternal interface. These changes are critical in promoting maternal tolerance. hCG is also able to increase the proliferation of uterine natural killer cells, while reducing the activity of cytotoxic peripheral blood natural killer cells. There are rare reports of autoantibodies directed against hCG or the luteinizing hormone/hCG receptor in women with recurrent miscarriage. These autoantibodies are more frequent in women with thyroid autoimmunity. This may explain the association between thyroid autoimmunity and impaired fertility. Downregulating these anti-hCG and anti-luteinizing hormone/hCG receptor autoantibodies may be helpful in some women with early miscarriage or recurrent failed in vitro fertilization.
[show abstract][hide abstract] ABSTRACT: Several different foods have been implicated in inducing the delayed and very significant vomiting and sometimes diarrhea that occurs in food protein-induced enterocolitis syndrome. While immunoglobulin E is not involved, the mechanism(s) that result in the food-induced gastrointestinal symptoms are unclear, although T cell activation has been considered. We report four cases of food protein-induced enterocolitis syndrome caused by different solid foods and without concomitant immunoglobulin E sensitization to milk and soya. Clinical and laboratory evidence of type I immunoglobulin E mediated food reactivity and food-induced T cell activation was absent in each case.
Case 1 concerned a 20-month-old South Asian boy who had experienced four episodes of severe vomiting with flaccidity since four months of age and two hours after consuming rice.Case 2 involved a nine-month-old Caucasian boy who had suffered three episodes of severe vomiting with flaccidity since six months of age and three hours after consuming wheat.The child in Case 3 was a 16-month-old Caucasian boy who had suffered three episodes of severe vomiting with flaccidity since nine months of age and two hours after consuming cod.Case 4 involved a 15-month-old South Asian boy who had suffered three episodes of severe vomiting since eight months of age and two hours after consuming chicken.
In children with recurrent marked delayed vomiting after the ingestion of specific foods and in whom bronchospasm, skin rash and angioedema are absent, food protein-induced enterocolitis syndrome should be considered. Skin prick testing and specific immunoglobulin E antibodies are negative and the mechanism of the vomiting is unclear. We speculate whether food protein-induced oligoclonal T cell activation may be present. This has similarities to various animal models and improvement may involve deletion of these T cells.
Journal of Medical Case Reports 06/2012; 6(1):160.
[show abstract][hide abstract] ABSTRACT: PURPOSE: Wegener's granulomatosis has been renamed granulomatosis with polyangiitis (WG/GPA). It is a systemic necrotizing granulomatous vasculitis that can affect particularly the lungs, sinuses and kidneys. We report two cases with anti-neutrophil cytoplasmic antibody (c-ANCA) positive WG/GPA whose initial presentations were in the form of both conductive and sensorineural hearing loss without systemic features. We contrast the reversal of hearing loss and prevention of disease progression with early recognition and treatment. METHOD: Presentation of two contrasting cases of WG/GPA. Changes in hearing was measured using a GSI 61 audiometer and British Audiology Guidelines. Serum ANCA were detected using indirect immunofluorescence. Proteinase 3 and myeloperoxidase antibodies were measured using a fluoroenzyme immunoassay. RESULTS: Persistent deafness, systemic disease and more aggressive therapy was required when the diagnosis of WG/GPA was delayed. CONCLUSION: WG/GPA should be considered in acute or sub-acute deafness presenting over days to weeks and even in the absence of systemic symptoms. A negative or weak ANCA with absent antibodies to serine proteinase-3 and myeloperoxidase should not exclude the possible diagnosis of WG/GPA and a high index of suspicion should be maintained.
American Journal of Audiology 06/2012; · 0.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recurrent miscarriage (RM) without an obvious identifiable cause may arise from excessive maternal T and natural killer (NK) cell activity against the trophoblast or early embryo. Impaired regulatory T cell function leading to increased pro-inflammatory Th17 and NK cell cytotoxicity may be central. Ongoing subclinical endometrial infection and/or inflammation with increased secretion of TNFα and stimulation of autoimmunity to heat shock proteins may also be contributory. Therapies with a varying theoretical basis and clinical evidence aimed at reducing excessive endometrial immune activity have been used non-selectively in women with RM with variable success. Recent work has now improved our understanding of the role of the different immune cells and proteins that are important at each stage of a normal pregnancy. The vulnerability of the early embryo to T and NK cell-mediated rejection suggests that immune-based therapies need to be maximally effective during early pregnancy. Targeting RM women with demonstrable T and NK cell activity may improve the overall clinical efficacy of these treatments. It may also prevent costly and possibly harmful use in women who are unlikely to respond, and make better use of scarce resources. This report describes the underlying principles behind the use of the different immune-based therapies. The broad evidence supporting their efficacy is also described, as are the possible adverse consequences. Suggestions are also made on how the maternal immune system may be positively modulated using current, widely available treatments that have minimal or no side effects.
Journal of Reproductive Immunology 12/2011; 93(1):41-51. · 2.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: The prevalence of vitamin D deficiency has been shown to be increased in many of the common arthritides. Importantly, vitamin D has significant immunomodulatory effects in addition to its role in calcium homoeostasis. Both aspects of its function have a major bearing on joint disease whether as part of an inflammatory arthritis or from wear and tear. While the exact mechanisms still require clarification, there is now compelling evidence that the hormonally active 1,25-dihydroxycholecalciferol vitamin D can reduce the activity of the proinflammatory Th1 and Th17 T cell subsets. Additionally, it is stimulatory of enhanced anti-inflammatory Th2 activity at the same time as promoting T regulatory cell activity. These various actions suggest that correcting vitamin D deficiency should be a important part of the management of all patients with joint disease. For the future, vitamin D analogues with enhanced immunomodulatory properties but with reduced ability to increase calcium are being investigated.
Rheumatology International 09/2011; 32(4):845-52. · 2.21 Impact Factor
[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: Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage (RM). The precise mechanism for this is unclear, as cross-reactivity between trophoblastic and maternal host autoantigens has not been demonstrated. In the antiphospholipid antibody syndrome, prothrombotic mechanisms are evident, along with direct inhibitory actions against trophoblastic activity. In many types of both systemic and organ-specific immunity, however, a disturbed T-helper cell profile is seen. This is also evident in women with RM. In both cases, reduced numbers of T regulatory cells have been reported. These are required to regulate excessive activity of the Th1 and the proinflammatory Th17 subsets that, when operating through excessive natural killer cell activity, may have antipregnancy effects. Checking for underlying autoimmunity is therefore a critical analysis in women with RM and future therapies will probably be aimed at correcting the deficiency of regulatory T cells or correcting excessive Th1 and Th17 function.
[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 investigate changes in the ratio of T-cell subpopulations expressing intracellular T helper1 (Th1) and T helper 2 (Th2) cytokines in women with a history of recurrent failed implantation under going in-vitro fertilization (IVF)-embryo transfer.
Twenty-eight peripheral blood samples were obtained at two time points, from 14 women undergoing IVF treatment; eight women with a history of recurrent failed implantation, who did not get pregnant in the index IVF cycle and six who had one or more previous successful IVF pregnancy and who became pregnant in the index IVF cycle. The proportion of lymphocytes expressing interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin 4 (IL-4) and the Th1:Th2 ratios of IFN-gamma:IL-4, and TNF-alpha:IL-4 in T helper cells was measured by flow cytometry, in samples obtained before commencing IVF treatment and in samples obtained after ovarian stimulation (on the day of oocyte retrieval).
In samples collected during oocyte retrieval, women with a history of recurrent failed implantation had a higher IFN-gamma:IL-4 and TNF-alpha:IL-4 ratio than the control group, (18.6+/-9.3 versus 6.47+/-1.68, P=0.009) and (39.1+/-15.7 versus 11.53+/-3.76, P=0.001) respectively. In women with a history of recurrent failed implantation the ratio of IFN-gamma:IL-4 and TNF-alpha:IL-4 at oocyte retrieval was higher than pre-treatment ratios (18.6+/-9.3 versus 12.01+/-9.8, P=0.018) and 39.10+/-15.7 versus 18.66+/-11.42, P=0.010) respectively, showing a Th1 bias. In women with a successful IVF the converse was true; the ratio at oocyte retrieval was significantly lower than pre-treatment ratios (6.47+/-1.68 versus 9.37+/-6.8, P=0.035) and 11.53+/-3.76 versus 18.60+/-12.9, P=0.027) respectively, representing a Th2 bias.
Women with a history of unexplained recurrent failed IVF treatment have a Th1 bias and this polarization is more enhanced following hormonal manipulations during IVF treatment. Comparing pre-treatment ratios of IFN-gamma:IL-4 and TNF-alpha:IL-4 to ratios obtained at oocyte retrieval may be clinically useful. Women with recurrent failed IVF have increasing ratios.
American journal of reproductive immunology (New York, N.Y.: 1989) 04/2008; 59(3):206-11. · 3.32 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