Immunologic alterations in xeroderma pigmentosum patients

Abstract

Nine xeroderma pigmentosum (XP) patients were investigated. In comparison to a normal control group the XP patients had a reduced OKT-4 lymphocyte subpopulation, reduced response of lymphocytes to phytohemagglutinin in autologous serum, and diminished delayed hypersensitivity skin reaction. The possible contribution of ultraviolet irradiation to the observed immunologic alterations, and the link of these alterations to the susceptibility of patients for malignant transformation is discussed. Cancer 58:219-221, 1986. ERODERMA PIGMENTOSUM (XP) is a rare autosomal X recessive disease. Patients are unable to repair ultraviolet (UV)-induced chromosomal damage and are succeptible to multiple pigmentous changes and malig-nancies on light-exposed areas.' Previous studies have demonstrated immunologic abnormalities in patients with XP. These include delayed rejection of skin grafts,2 reduced induction of lymphocytes by phytohemagglutinin (PHA) due to an inhibitory serum f a ~ t o r , ~-~ and combined immunodeficiency in one patient .5 Studies on mice have demonstrated alteration of the immune system secondary to UV irradiation.6-8 Such irradiation promoted the development of skin tumors, probably due to induction of suppressor T-cells, which delayed the antitumor response. Later studies in normal volunteers disclosed alterations of T-lymphocyte subsets secondary to UV irradiati~n.'.'~ As a result of the relationship between the immune system and UV irradiation, and due to the fact that XP patients are extremely UV-sensitive, we decided to investigate whether the immunological changes in XP patients might follow the pattern of those observed in normal controls after UV irradiation. Materials and Methods XP patients were diagnosed each by two independent dermatologists. Immunoglobulins were quantified by nephelometry" and compared to a control group of normal individuals. Delayed hypersensitivity (DHS) skin testing was performed by the intracutaneous injection of 0.1 ml of the following four recall antigens: purified protein derivative (PPD) (Connaught Laboratories), Candida (Hollister Stier Laboratories), trichophyton (Hollister Stier Laboratories) and streptokinase/streptodornase (SK/SD) (Lederle Laboratories). Testing was first performed with low concentrations 5 TU, 1 / 1000, 1 / 1000, and 10/2.5, respectively. The response was considered positive when 24 to 48 hours after injection, an induration of more than 5 mm was observed. l2 Lymphocyte transformation was performed by the method of Cunningham-Rundles et al., l 3 and mononu-clear cells were isolated by the method described by Bo-yum.14 Cultures were performed in triplicate, and dose response curves were established with 17.5, 4.4, and 1. I, pg/culture of PHA-P-Difco (Difco Lab, Detroit, MI), and 25, 17.5, 2.5, and 0.5 yglculture of pokeweed mitogen (PWM), respectively. Cultures were performed in 10% fe-tal calf serum (FCS) and concomitantly in 10% autologous serum. The cultures were harvested after 96 hours, with maximal stimulability exceeding 1 5000 CPM consider...

Impaired interferon production and natural killer cell activation in patients with the skin cancer-prone disorder, xeroderma pigmentosum.

“…In addition to the DNA repair defects found in all XP patients, there have been a variety ofcellular immune abnormalities noted in isolated XP patients: decreased delayed-type hypersensitivity reactions (impaired responses to intradermal recall antigens and decreased dinitrochlorobenzene sensitization), decreased T-cell proliferative responses to mitogens, decreased CD4/CD8 ratio, and one report each of severe combined immunodeficiency and systemic lupus erythematosus ( 15,(18)(19)(20)(21)(22)(23)(24)(25). Norris et al (26,27) reported decreased NK cell activity in five patients with XP, when compared to normal controls, and in patients with trichothiodystrophy or Cockayne syndrome.…”

Ultraviolet Radiation-Induced Impairment of Tumor Rejection Is Enhanced in Xeroderma Pigmentosum A Gene-Deficient Mice

“…Although CHS was induced in non-irradiated XPA mice as well as wild-type mice, UVB-induced local and systemic immunosuppressions were greatly enhanced in XPA mice (Miyauchi-Hashimoto et al, 1996). There are some studies that patients with XP have defects in cell-mediated immunity such as impaired cutaneous responses to recall antigens and a contact sensitizer (Morison et al, 1985;Wysenbeek et al, 1986;Goldstein et al, 1990). Our studies using XPA mice suggested that the immunologic dysfunction in XP patients is not innate but acquired possibly after exposures to the sunlight.…”

Combined Immunodeficiency Associated with Xeroderma Pigmentosum

“…We are aware of only one report ofa child who had agammaglobulinemia and abnormal T cell response to PHA (7). Although the etiology of the immunologie alterations in XP is unknown, it is hypothesized there is a relationship between UV irradiation and immunologic changes, and that these changes may also play a role in the development of UV-induced skin tumors (5).…”