Characteristics associated with significantly worse quality of life in mycosis fungoides/Sézary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. AIM: To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. METHODS: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. RESULTS: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (ß = 8·61; P = 0·003) and alopecia (ß = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19-3·89] and emotions (OR 1·88, 95% CI 1·09-3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. CONCLUSIONS: HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients. What's already known about this topic? Cross-sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sézary syndrome (SS) have shown significant impairment in health-related quality of life (HRQoL). Previous studies on assessing gender-specific differences in HRQoL in MF/SS are conflicting. More advanced-stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS. In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema. MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well-being.

Characterization and immunogenicity of EX880, a Salmonella typhi Ty21a-based clone which produces Vibrio cholerae O antigen.

EX645 is a derivative of Salmonella typhi Ty21a which carries a plasmid specifying production of Vibrio cholerae O antigen. When cultured with exogenous galactose to overcome the galE defect of the vector, EX645 also synthesizes S. typhi O antigen, and this can result in the masking of the shorter V. cholerae O antigen on the bacterial surface. To determine whether the potential for such masking at least partly underlies the inconsistency of anti-V. cholerae responses elicited by EX645, a derivative of this strain has been isolated, characterized, and tested for immunogenicity in human volunteers. EX880 has an rfb defect which prevents synthesis of S. typhi O antigen, and consequently V. cholerae O antigen is still detectable on the surface of the clone following growth in the presence of galactose. Compared with EX645, EX880 more consistently elicited significant rises in serum bactericidal antibody levels, although individual responses within a cohort still varied widely.

Autoantibody-specific suppressor cells are elicited by membrane components of rat RBC independently of circulating autoantibodies but TNP-specific suppressors are not elicited by TNP-rat RBC.

Erythrocyte autoantibodies and autoantibody-specific suppressor cells are elicited in mice injected with rat erythrocytes. Here it is shown, first, that modified rat erythrocytes elicit suppressor cells independently of autoantibody production. Haemoglobin-free membranes of rat erythrocytes, but not soluble lysates of rat erythrocytes, elicited autoantibodies and suppressor cells. Solubilization of these rat erythrocyte membranes with solutions of Triton-X-114 produced membrane fractions which induced autoantibody-specific suppression in the absence of detectable autoantibody production. These results are compatible with the view that the activation of suppressor cells in this model involves recognition of structures on the rat erythrocytes. Secondly, trinitrophenyl (TNP) was attached to rat erythrocytes in various doses in attempts to make the immunogenicity of TNP similar to that of the cross-reactive determinants on rat and mouse erythrocytes, to determine whether TNP-specific suppressor cells were produced. The results show that at various doses of TNP, including those at which antibody production to TNP could not be detected, rat erythrocytes coated with TNP induced autoantibody-specific suppressor cells but not suppressor cells with specificity for antibodies to TNP.

Experimental erythrocyte autoimmunity. IV. Differential susceptibility to irradiation of suppressor cells for anti-rat RBC antibodies and suppressor cells for mouse RBC autoantibodies.

Mice injected with rat erythrocytes (RBC) produce RBC autoantibodies and antibodies against rat RBC. Transfer of spleen cells from autoantibody-producing mice to syngeneic recipients before the series of rat RBC injections causes a significant delay in autoantibody production although the response against rat RBC is elevated. Here it is shown that antibodies against rat RBC are markedly increased in recipients exposed to 350 rad of whole-body irradiation before transfer of spleen cells and the injections of rat RBC. In contrast, autoantibody production remained significantly suppressed. This shows that the anti-rat RBC response is regulated, at least in part, by cells in normal mice that are abrogated by 350 rad of whole-body irradiation.

Suppression of autoantibodies is specific for the foreign antigens inducing the autoimmunity.

Mice injected with rat erythrocytes produce erythrocyte autoantibodies and suppressor cells that specifically inhibit the autoimmune response without inhibiting the net production of antibodies against rat erythrocytes. Here it is shown that the suppressor cells bind preferentially to monolayers of rat erythrocytes rather than to erythrocytes from mice or sheep. Suppressor populations depleted of B cells, and cells that adhered to monolayers of rat erythrocytes, lost the ability to suppress the production of autoantibodies in normal mice injected with rat erythrocytes. In contrast, suppressor populations depleted of B cells and cells that adhered to sheep erythrocytes or mouse erythrocytes retained suppressor activity. From these results it is suggested that the regulation of autoantibody production by the suppressor cells in this model may be part of a normal system by which antibody responses to foreign antigens are regulated, and not a unique homeostatic mechanism by which harmful autoimmune responses are eliminated.