Premature ovarian failure. II: Considerations of cellular immunity defects.

Twenty-three patients with premature ovarian failure (POF), were investigated on the basis of cell-mediated immunity. An increase in T-cells and especially T-helper cells was found in the group of POF patients, while T-suppressor cells and B-cells did not exceed the counts compared to healthy controls matched for age and sex. The macrophage migration inhibition factor (MIF) assay showed a decreased activity towards Haemophiles influenza. Candida albicans and Varidase antigens in the POF group. Levels of immunoglobulins (IgG, IgA, IgE and IgM) did not exceed the normal levels. The relationship between the hormonal status of POF patients and their immunological profile is discussed.

Abnormal monocyte chemotaxis in patients with chronic purulent rhinosinusitis: an effect of retroviral p15E-related factors in serum.

Earlier we reported that about 60% of patients suffering from unexplained relapsing of chronic purulent rhinosinusitis show a defective T cell-mediated immunity to commensal microorganisms of the upper respiratory tract. The monocyte chemotactic responsiveness was assessed in 40 of these patients by means of the polarization assay. Impaired FMLP-induced monocyte polarization was found in 26 of the 40 patients tested. The defective chemotactic responsiveness could be explained by a p15E-related factor detectable in the serum of the patients: addition of serum fractions less than 25 kD to healthy donor monocytes resulted in an inhibition of polarization; a monoclonal antibody directed against p15E neutralized this inhibitory effect. In individual patients, a decreased monocyte polarization correlated well with the presence of this p15E-related factor in serum, as well as with defective T cell reactivity.

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.

Parameters of T cell mediated immunity to commensal micro-organisms in patients with chronic purulent rhinosinusitis: a comparison between delayed type hypersensitivity skin test, lymphocyte transformation test and macrophage migration inhibition factor assay.

In 75 patients with unexplained chronic purulent rhinosinusitis T cell mediated immunity to three micro-organisms frequently colonizing the human upper respiratory tract, viz. Haemophilus influenzae, streptococci and Candida albicans, was assessed. Delayed type hypersensitivity (DTH) skin test reactivity was measured in vivo, whereas the blastogenic responsiveness (lymphocyte transformation test; LTT) and lymphokine production (e.g. migration inhibition factor; MIF) of the lymphocytes upon antigen stimulation were measured in vitro. MIF was assayed with a recently developed test system using the human monocytoid cell-line U937 as indicator cells in agarose microdroplets. Two-thirds of the 75 patients tested showed a defective DTH response to one or more of the microbial antigens; this contrasted to the findings in 25 healthy subjects, of whom over 90% showed a positive DTH reaction to any of the three antigens. PHA skin tests were entirely normal in both patients and healthy controls. Microbial antigen-specific LTT responses fluctuated considerably in time from strongly positive to negative and vice versa in healthy individuals as well as in patients. In general however, blastogenic responses in patients were comparable to or even higher than those of healthy persons. In the MIF assay, lymphocytes of all healthy individuals tested showed production of MIF upon stimulation with all three antigens; this again contrasted to two-thirds of the patients, whose lymphocytes showed a defective MIF production. Fluctuations of MIF-production in time could not be established and a very good correlation existed between the data obtained in the MIF assay and those of the DTH skin tests. These results indicate that apart from skin testing, the MIF assay seems to be the most suitable parameter to assess defects in T cell reactivity towards microbial antigens. These defects exist in two-thirds of our patients suffering from chronic purulent rhinosinusitis.

The use of somatic antigen of Haemophilus influenzae for the monitoring of T cell-mediated skin test reactivity in man.

To investigate its usefulness as a skin test antigen, Haemophilus influenzae somatic antigen was tested in 28 healthy individuals, both in soluble and aggregated form. All subjects were found to possess specific antibodies against H. influenzae of both IgG and IgM subclass, thus showing their previous exposure to this commensal micro-organism. The somatic antigen in solution was found to be a poor antigen for eliciting a delayed hypersensitivity skin response: only 2 out of 16 subjects reacted with a positive DTH pattern. In contrast, 25 out of 28 persons showed a positive DTH pattern when somatic antigen was used in aggregated form. Two types of DTH reaction patterns could be detected (in a ratio of approximately 3:2), viz. those with an early (24 h) and those with a late (48 h) maximal swelling. Histology of 3 early and 1 late DTH reaction showed perivascular infiltrates of mainly Thelper/Tinducer lymphocytes. Hardly any basophils were seen. One negative skin test, biopsied at 6 h, showed no signs of Arthus reactivity. It can be concluded that skin tests using the aggregated form of the somatic antigen of H. influenzae are useful for assaying specific T-cell-mediated reactivity in man.