In vitro studies in nickel allergy: diagnostic value of a dual parameter analysis.

A comparison was made between the diagnostic value of assaying nickel-induced lymphocyte proliferation (lymphocyte transformation test, LTT) and migration inhibition factor (MIF) production in nickel contact sensitivity. Although lymphocyte proliferation was significantly increased in the group of patients with skin test reactivity to nickel, positive LTT were also frequently found in skin test-negative subjects: in 63% of subjects with and in 30% of subjects without a history of metal allergy. This would limit the value of the LTT as an in vitro correlate of skin test reactivity. However, in certain patients positive lymphocyte transformation may reveal nickel sensitization at a time of undetectable skin reactivity. Data obtained with the macrophage migration inhibition test (MMIT) showed a good correlation with nickel patch test reactions. Accurate determination of MIF became feasible by using cells from the human monocytoid cell line U937 as target cells in a microdroplet agarose assay. Using this MMIT, positive reactions occurred in 13% of the healthy controls and false-negative reactions were found in 26% of patients with positive skin test reactivity to nickel. As LTT and MMIT data appeared to be only weakly correlated in the individuals tested, a dual parameter analysis was performed. An excellent correlation [p = 1.8 (10(-8]] was found between skin test and in vitro reactivity for individuals with matching in vitro results (60% of all individuals tested). In those individuals with discordant in vitro data, skin testing will remain indispensable for diagnosing nickel allergy.

T-suppressor cell defects in euthyroid nonendemic goitre.

Recently it has been suggested that a substantial number of nonendemic goitre cases can be considered as organ-specific autoimmune disorders of the thyroid. Circulating immunoglobulins, probably receptor autoantibodies, stimulating guinea pig thyroid growth in vitro (TGI) can be found in 2/3 of such patients. Defects in the regulatory balance between T-helper (Th) and T-suppressor (Ts) cells have been described in other thyroid autoimmune diseases, such as Graves' disease and Hashimoto goitre. Such defects are thought to play a role in the loss of control over thyroid autoantibody producing B cells. To investigate whether Ts cell defects can also be found in nonendemic euthyroid goitre, we studied their number and function in 15 of such patients. All patients were clinically euthyroid. Eleven were positive for TGI. Circulating T cells, Th cells and Ts/cytotoxic cells were enumerated using monoclonal antibody techniques (OKT3, Leu3a and OKT8, respectively). Suppressor cell function was assessed employing a proliferation assay in which a short-lived population of such cells was removed by a 24 h preculture. A significant difference was found between patients and controls regarding the Leu3a+/OKT8+ cell ratio: 2.74 (SD 0.94) in patients vs 1.75 (SD 0.38) in controls (P less than 0.01); the disturbed ratio was mainly due to a decrease in the percentage of OKT8+ cells. The functional Ts cell assay also showed a defect of patient lymphocytes: patient removal index (SRI) was 1.5 (SD 1.0) vs an index of 2.6 (SD 1.2) for healthy controls (P less than 0.05). A fair correlation between the numerical and functional data on Ts cells was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of carbimazole-induced intrahepatic cholestasis. An immune-mediated reaction?

A patient is described with cholestatic hepatitis following the use of carbimazole. A liver biopsy specimen showed intracanalicular cholestasis and some mononuclear cell infiltrate in the portal triades, consistent with drug toxicity; indications of an autoimmune or viral pathogenesis were absent. Rechallenge with the drug precipitated jaundice and disturbed liver function once more. Carbimazole induced a blastogenic response of patient lymphocytes in vitro. Both may suggest the involvement of an immune-mediated reaction, especially as it has been shown that sensitized lymphocytes may produce a cholestatic factor on stimulation with antigen.

Penicillin allergy and the relevance of epicutaneous tests.

Epicutaneous tests with penicillins are important in the evaluation of penicillin allergy in patients who have shown a delayed urticarial or maculo-papular rash after the administration of penicillin derivatives. Of 23 patients who showed positive epicutaneous tests only 5 also showed immediate-type reactivity upon subsequent intracutaneous tests with the major determinant of penicillin. Moreover, patients with positive epicutaneous tests were evidently immunologically reactive on penicillins, since lymphocytes from 14 out of 17 patients showed increased DNA synthesis induced by penicillin G and ampicillin in vitro. The performance of epicutaneous tests with various penicillin derivatives is recommended as a first step in establishing penicillin allergy, because it is a safe method and because an extra group of sensitized patients is detected.

Induction of contact sensitivity to a broad variety of allergens with haptenized macrophages.

Using guinea pigs an analysis could be made of various aspects of contact sensitivity (CS) induced by subcutaneous injection of syngeneic haptenized macrophages (oil-induced peritoneal exudate cells, PEC) as compared to epicutaneous sensitization. Very little PEC-bound hapten (dinitrochlorobenzene, or oxazolone) is needed for optimum sensitization. Nevertheless, both sensitization methods induce a state of CS that may last for over 6 months, give rise to hapten-specific antibodies with a similar isotype distribution, and show susceptibility to cyclophosphamide pretreatment. In addition, time courses and microscopic appearance of skin test reactions after either way of sensitization are identical. CS to a broad variety of physicochemically different antigens, including nickel, penicillin, and acrylates, is readily induced by syngeneic PEC, haptenized following a standardized procedure. As Freund's complete adjuvant is known to cause serious side effects like ulceration and long-lasting granuloma formation, immunization with haptenized PEC should now be considered as a clean and effective alternative in experimental CS studies.

Angry back or the excited skin syndrome. A prospective study.

Allergens eliciting weak positive reactions were retested to ascertain their reproducibility. Weak positive patch test reactions, concomitant to other weak or strong positive reactions, were retested after 3 weeks in 61 patients. 79 reactions were retested; 35 (44.3%) were negative. Allergens which are marginal irritants, e.g., formaldehyde, often gave weak positive reactions which were lost at retesting. In patients without dermatitis but with several strong positive reactions, lost reactions were frequently encountered, suggesting that strong reactions induced a state of hyperirritability. False positive reactions were often found in the proximity of strong reactions. We attempted to develop a nonspecific irritant (sodium lauryl sulfate) as a hyperirritability marker. A correlation between the score of this test and false positive reactions was not found. It is concluded that weak positive reactions should not be accepted as a proof of sensitization. The allergens eliciting these reactions should be retested at a later date.

Depression or enhancement of skin reactivity by inflammatory processes in the guinea pig.

An animal model for the excited skin syndrome was developed in the guinea pig. Hyperirritability of the skin could be induced by immunization with Freund's complete adjuvant (FCA). This hyperirritability was evident from the enhancement of both patch test reactions to an irritant (sodium lauryl sulfate) and open epicutaneous test reactions to a contact sensitizer (2,4-dinitrochlorobenzene). The skin tests were performed at sites other than those pretreated with FCA. Maximum enhancement was observed in a period 3-5 weeks after FCA immunization. A similar but less marked hyperirritability could be induced by eliciting a localized chronic croton oil dermatitis. The period of hyperirritability induced by FCA or croton oil was preceded by a short period (1-14 days) of depressed skin reactivity.