Delayed‐type allergy to cobalt—comparison of a flow cytometric lymphocyte proliferation test with patch testing

Abstract

Background The patch test is the standard procedure for diagnosing delayed‐type sensitization. If a patch test is not possible, the flow cytometric lymphocyte proliferation test (LPT), which determines the number and type of cells responding to a specific antigen in vitro, might be considered as an alternative. Objectives Our aim was to establish a flow cytometric LPT for the detection of delayed‐type allergic responses to cobalt, and to determine the correlation between stimulation indices (SIs) in LPT and the grade of patch test reactions. With the patch test as a diagnostic reference, we also assessed the sensitivity and specificity of the LPT. Methods Fifty‐four patients patch tested with the baseline series including cobalt (CoCl2) were additionally tested with the flow cytometric LPT with CoCl2. Results There was a significant correlation between the results of both tests: rs = 0.43; P = .001. The LPT with CoCl2 showed a sensitivity of 52.6% and a specificity of 85.7%. Corresponding to the low sensitivity of the LPT, high likelihood ratios for a positive patch test reaction were reached only in cases of strong lymphocyte proliferation (SI ≥ 10). Conclusions In cases of clearly increased SIs, the flow cytometric LPT with CoCl2 gives relevant diagnostic information, and represents a valuable alternative to patch testing.

Memory T helper cells identify patients with nickel, cobalt, and chromium metal allergy

“…The nonheated inactivated autologous serum is indeed an attractive approach to optimizing the LPT; however, the influencing factors in the allergic individuals' autologous serum are still unknown, making, for example, fluctuations of these factors a potential problem. In concordance with previous reports, 14–16,32 we observed the Th cell as the dominant circulating cell type reacting to metals. Detailed analysis of the metal‐reactive Th cells revealed high expression of CD4 and CD45RO.…”

“…This could indicate that there is indeed a cross‐reactivity on the T‐cell level of the Ni‐ and Co‐reactive patients—however, more studies such as that recently published by Kapp et al 26 are needed. As reported by others, 16 detecting Co‐reactive cells by the LPT was less accurate than detecting Ni‐reactive cells. Whether this is attributable to false‐positive Co patch test 39 or merely an overall lower relative frequency of Co‐specific Th cells needs to be investigated.…”

“…However, a high degree of variation in the accuracy of the more recently published Ni LPT studies, using radioactive incorporation, is observed (Supporting Information S5). Although flowcytometric LPT for Ni and Co are scarce, [14][15][16] an overall tendency of improved sensitivity and specificity is seen compared with LPT studies using radioactive incorporation (Supporting Information S5). Moreover, in this study, increased accuracy was identified when analysing the subpopulation of skin-homing Th cells compared with the whole population of Ni-reactive memory Th cells with a sensitivity of 100% versus 69% and specificity of 92% versus 85%, respectively.…”

“…Combined with multiparameter single-cell analysis by flow cytometry, carboxyfluorescein succinimidyl ester (CFSE) labelling 13 is a nonradioactive alternative for detecting proliferating cells. Flow cytometric LPT with staining with CFSE was previously described to identify patients reactive to Ni 14,15 and Co 16 but not for Cr in patch tests. Although flow cytometric LPT with the gating of T helper (Th) cells has improved the test's specificity, information about the specific metal-proliferating cells is lacking.…”

A literature review and expert consensus statement on diagnostics in suspected metal implant allergy

“…However, recent attempts to better standardize it or to increase its specificity have been published. [40][41][42][43][44] Another controversial issue is preoperative subcutaneous implantation of material probes as a biocompatibility assay. Beecker et al had suggested to use subcutaneous metal implant probes to predict complications following insertion of knee implants.…”