Is the variability of nickel patch test reactivity over time associated with fluctuations in the systemic T-cell reactivity to nickel?

BACKGROUND: Patch test reactivity to nickel varies over time. To what extent this variation is associated with fluctuations in the T-cell reactivity to nickel is not known. OBJECTIVES: Our aim was to investigate the relationship between variation over time in the patch test and the systemic T-cell reactivity to nickel. METHODS: Patients (n = 15) with a history of contact allergy to nickel were subjected to three consecutive patch tests at 3-month intervals, utilizing NiSO4 at 10 concentrations ranging from 0.0032% to 12.5%. Prior to each patch test, blood mononuclear cells were analysed for T-cell reactivity to nickel by interleukin (IL)-4 and IL-13 enzyme-linked immunospot assay. RESULTS: Eleven patients reacted positively in all three patch tests, two patients reacted in one or two tests and two remained negative. All 13 positive patients displayed variability over time, in terms of the lowest dose of nickel to which they responded. Also the cytokine response to nickel varied over time but the patients' mean cytokine response was positively correlated with their mean patch test reactivity (r(s) = 0.70, P < 0.01 for IL-4; r(s) = 0.78, P < 0.001 for IL-13). However, although the changes over time in patch test reactivity and the cytokine responses to nickel displayed a similar pattern in many patients, there was no significant correlation between the individuals' variation over time in vivo and in vitro. CONCLUSIONS: The overall magnitude of the T-cell reactivity to nickel and the patch test reactivity are closely associated but fluctuations in the systemic T-cell reactivity cannot be singled out as the major cause of longitudinal variability in nickel patch test reactivity.

Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals.

Nickel (Ni), the main cause of contact allergy to metals, induces in vitro production of both Th1- and Th2-type cytokines in peripheral blood mononuclear cells (PBMC) from allergic subjects. Because the knowledge of the cellular immune response to other metals involved in contact allergy has been limited, we investigated the cytokine profile induced by Ni, cobalt (Co), chromium (Cr), palladium (Pd) and gold (Au) in PBMC from patients with patch test reactivity to the respective metals. PBMC from patients with patch test reactivity to Ni, Co, Cr, Au and/or Pd (n = 31) and non-allergic controls (n = 5) were stimulated in vitro with corresponding metal salts. Th1- [interleukin (IL)-2 and interferon (IFN)-gamma] and Th2- (IL-4 and IL-13) type cytokine responses were measured by enzyme-linked immunospot (ELISpot) and/or enzyme-linked immunosorbent assay (ELISA). All metals induced a mixed Th1- and Th2-type cytokine production in PBMC from individual patients with patch test reactivity to the corresponding metal, but not in control PBMC. Significantly higher responses in the patient versus controls were found for Cr (IL-2 and IL-13), Pd (IL-2 and IL-4), Au (IL-13 and IFN-gamma) (all P < 0.05) and Ni (all four cytokines; P < 0.01) but not Co. Overall, 71% (37/52) and 89% (81/91) of the positive and negative patch test reactivities to metals, respectively, were matched by the in vitro reactivity. In conclusion, our data suggest that sensitization to Co, Cr, Pd and Au results in a cellular immune response of a character similar to the mixed Th1- and Th2-type cytokine profile shown previously to be induced by Ni.

Nickel-induced IL-10 down-regulates Th1- but not Th2-type cytokine responses to the contact allergen nickel.

Whereas the involvement of Th1- and Th2-type cytokines in contact allergy to nickel (Ni) is well documented, the role of the regulatory cytokine IL-10 is less clear. We therefore investigated the impact of IL-10 on Ni-induced Th1- (IFN-gamma) and Th2-type (IL-4 and IL-13) cytokine responses in human peripheral blood mononuclear cells (PBMC). PBMC from 15 blood donors with reactivity to Ni (Ni-PBMC) and 8 control donors devoid of reactivity (control PBMC) were stimulated with Ni and the frequency of cytokine-producing cells and the levels of secreted cytokines were analysed by ELISpot (IL-4, IL-13 and IFN-gamma) and ELISA (IL-10, IL-13 and IFN-gamma), respectively. The Ni-induced response was further assessed in the presence of recombinant IL-10 (rIL-10) or neutralizing antibody to IL-10 and the phenotype of the Ni-specific cytokine-producing cells regulated by IL-10 was determined by cell depletion experiments. Ni induced IL-10 production in Ni-PBMC (mean, (range); 33.1 pg/ml (0-93.4 pg/ml)) but not control PBMC (2.2 pg/ml (0-14.9 pg/ml)) (P = 0.002). Ni also induced significant production of IL-4, IL-13 and IFN-gamma that correlated with the IL-10 response. Addition of rIL-10 down-regulated the Ni-induced production of all cytokines but with a more pronounced effect on IFN-gamma. However, neutralization of Ni-induced IL-10 enhanced the levels of IFN-gamma induced by Ni (P = 0.004) but did not affect the number of IFN-gamma-producing cells or the production of other cytokines. Cell depletion experiments suggested that the Ni-specific IFN-gamma (and Th2-type cytokine) producing cells were CD4(+) T cells. The impact of IL-10 on Ni-induced IFN-gamma responses by CD4(+) T cells suggests that an important role of IL-10 in vivo is to counteract the allergic reactions mediated by Th1-type cytokines.

Nickel elicits concomitant and correlated in vitro production of Th1-, Th2-type and regulatory cytokines in subjects with contact allergy to nickel.

Nickel (Ni2+) elicits production of functionally distinct cytokines in vitro, but the relation between the cytokine profile and the degree of the allergic reaction in vivo needs to be better defined in order to improve the understanding of the immunological mechanisms involved in contact allergy and to facilitate development of in vitro diagnostics. The aim of the study was to define Th1-type [interferon-gamma (IFN-gamma)], Th2-type [interleukin-4 (IL-4), IL-5 and IL-13] and regulatory (IL-10) cytokine responses to Ni2+ in peripheral blood mononuclear cells (PBMC) from subjects with varying patch test reactivity to Ni2+. The study included subjects with strong (+3), moderate (+2), weak (+1) or negative (controls) patch test reactivity to Ni2+ (n = 10 per group). All +3 and +2 subjects but only three +1 subjects had a clinical history of contact allergy to Ni(2+). Cytokine production of PBMC stimulated with Ni(2+) was determined by enzyme-linked immunospot and/or enzyme-linked immunosorbent assay. Ni2+ elicited significant production of all cytokines in PBMC from patch-test-positive subjects versus controls with a positive correlation between each cytokine and the patch test reactivity as well as with other cytokines. More subjects responded to Ni2+ above cut-off values with Th2-type cytokines as compared with IFN-gamma or IL-10; 100% of +3, 80% of +2, 50% of +1 and 0% of control subjects displayed reactivity to Ni2+ based on IL-4 and IL-13 assays. Despite the prevailing view of Ni2+ allergy as a type-1-mediated condition, the in vivo reactivity to Ni2+ correlated with a mixed Th1-type, Th2-type and regulatory cytokine response to Ni2+in vitro. The results accentuate the importance of type 2 responses in contact allergy and also demonstrate that IL-4 and IL-13 are reliable markers for Ni2+ allergy.

Malaria infection in pregnancy and its effects on haemoglobin levels in women from a malaria endemic area of Fako Division, South West Province, Cameroon.

Anaemia in pregnancy has been associated with maternal morbidity and mortality and is a risk factor for low birthweight. The importance of malaria as a major cause of anaemia in pregnancy in malaria endemic areas has not been fully elucidated. In two cross-sectional studies of pregnant women at antenatal enrolment and at delivery, we determined the prevalence of anaemia and assessed some risk factors associated with anaemia such as malaria parasitaemia and parity, in women from a malaria endemic area of south western Cameroon. Of the 1118 women whose Hb levels were analysed at first antenatal enrolment, 68.9% were anaemic (Hb<11.0 g/dL) although only 1.3% were severely anaemic (Hb<7 g/dl). At delivery, 69.9% (485/694) of the parturient women were anaemic with 4.3% having severe anaemia. The mean haemoglobin (Hb) level of the pregnant women at enrolment and at delivery was not significantly different. The mean Hb level of malaria parasite positive pregnant women (P=0.0001) and parturient women (P=0.0001) were significantly lower than those who were malaria parasite free. Similarly, the mean Hb level of primigravidae at antenatal enrolment (P=0.0001) and at delivery (primiparae; P=0.0001) was markedly lower than that of multigravidae or multiparae, respectively. Of the anaemic cases, 52.1% were malaria positive while 47.9% were malaria free at enrolment. By contrast, 36.9% (179/485) of the anaemic cases were associated with maternal malaria parasitaemia while 37.3% (174/466) were associated with placental malaria parasitisation. Thus at delivery, anaemia was more common in women without malaria parasitaemia (P=0.0003) or whose placentas were malaria free (63.1% vs 36.9%; P<0.05). The prevalence of anaemia was significantly higher (OR=2.399; P=0.001) in mothers whose peripheral blood and placental biopsy were free of malaria parasites (69.9%) than in those whose peripheral and placental samples had malaria parasites. The mean birthweight and placental weights of newborns of mothers with and without anaemia were similar. In addition, there was no association between maternal anaemia and the incidence of low birthweight. Our study demonstrates a high prevalence of mild to moderate anaemia amongst the study population with relatively low incidences of severe anaemia. Furthermore, at delivery >50% of the anaemic cases were not associated with maternal or placental malaria parasitaemia suggesting the existence of other causes of anaemia in this community. This observation is important in developing a strategy for controlling anaemia in the community.