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The epithelia constitute a major barrier to the environment and provide the first line of defense against invading microbes. Antimicrobial peptides are emerging as participants in the defense system of epithelial barriers in general. Originally we isolated the human antimicrobial peptide LL-37 from granulocytes. The gene (CAMP or cathelicidin antimicrobial peptide) coding for this peptide belongs to the cathelicidin family, whose members contain a conserved pro-part of the cathelin type. The human genome seems to have only one gene of this family, whereas some mammalian species have several cathelicidin genes. In the present work we demonstrate up-regulation of this human cathelicidin gene in inflammatory skin disorders, whereas in normal skin no induction was found. By in situ hybridization and immunohistochemistry the transcript and the peptide were located in keratinocytes throughout the epidermis of the inflammatory regions. In addition, the peptide was detected in partially pure fractions derived from psoriatic scales by immunoblotting. These fractions also exhibited antibacterial activity. We propose a protective role for LL-37, when the integrity of the skin barrier is damaged, participating in the first line of defense, and preventing local infection and systemic invasion of microbes.

Orosomucoid (ORM) types were studied by isoelectric focusing and immunoblotting in 175 psoriatic patients and 2,217 blood donor controls from the county of Västerbotten in northern Sweden. There was a significant difference between patients and controls with respect to the distribution of ORM types (p = 4 x 10(-4)). The ORM1 1 type showed an increased frequency among the psoriatic patients (p = 1 x 10(-4) with a relative risk of 1.82 (95% CI:1.34-2.48).

Topical corticoids remain the mainstay of treatment for mild psoriasis. In recent years certain valuable modifications of this mode of treatment have emerged. Clobetasol propionate was found to induce the highest immediate response if applied as intensive pulse therapy and possibly also to induce longer remissions than other compounds. Once-daily application of betamethasone dipropionate in optimized vehicle and mometasone furoate were at least as effective as repeated applications of several other compounds. There are indications of a dissociation of potency and side effects for mometasone furoate. Thus, corticoid therapy now can be tailored to suit more closely the needs of the patients than was possible previously.

A possible association between psoriasis and cancer was investigated by linking the Swedish Psoriasis Association's membership registry to the Swedish Cancer Registry. The population studied was 20,328 living persons. Since 1958 a cancer was recorded in 520 of them. The expected number, based on the prevalence of cancer in Sweden, was 540. Among 43 cancer sites for men and 46 for women selected primarily for analysis, a significant association with psoriasis was found only in two types of cancer. For male breast cancer the observed number was 4 and the expected number was 0.58, and for female kidney cancers the observed number was 17 and the expected number was 6.1. The statistically significant excess risk found for these two forms of cancer may be the result of multiple statistical testing rather than a phenomenon of true biologic significance. Thus psoriasis patients seem not to deviate from the general population with regard to cancer prevalence.

Several previous studies have demonstrated a chemotactic factor for white blood cells in extracts from psoriatic scales. In the present work, the question was studied whether chemotaxis is a primary or a secondary event in the development of a psoriatic lesion. The migration-stimulating properties of polymorphonuclear leukocytes of different extracts were determined by means of a modified Boyden technique. Aqueous extracts of psoriatic scales were good stimulators of migration of both autologous and homologous leukocytes. Uninvolved skin adjacent to psoriatic plaques (perilesional skin) has previously been shown to differ from control skin in various respects. Extracts of such perilesional skin of psoriatic patients did not have migration-stimulating properties. This result indicates that chemotaxis is a secondary event in the pathogenesis of psoriasis.

Extracts of psoriatic scales from patients with chronic plaque psoriasis and of normal human post-mortem skin were tested for their effects on the migration of healthy human mononuclear cells in a modified Boyden chamber. A preparation of cells containing 12-32% monocytes was obtained from whole blood by a density gradient technique. The cells were allowed to migrate through a polycarbonate filter towards various dilutions of the two types of extract, a known chemoattractant or towards buffer alone. There was enhancement of migration towards psoriasis scale extract, with significant differences only at the stronger concentrations tested. The results suggest that scales taken from stable plaque psoriasis contain an extractable water-soluble factor which stimulates the movement of peripheral blood mononuclear cells.

In a study on genetic markers (22 HLA antigens, 6 blood group types, 3 serum groups and 3 red cell enzymes) in psoriatic patients the following statistically significant differences were found between patients and controls: 1) The HLA factors B13 and Bw17, the Lewis blood group Le(a-b-) and the blood group factor A were overrepresented among the patients. A decrease in the frequencies of the HLA factors B7 and B8 was noted, confirming several similar findings by other investigators. 2) In the Ss (MNSs), C3 and haptoglobin (Hp) systems the psoriatic patients showed a decreased frequency of heterozygotes. 3) Among patients with continuous symptoms the blood group factor A and the blood group Fy (a+b-) were overrepresented. 4) Patients with late onset of psoriasis showed an increase in the blood group (Fy(a+bb-) and a decrease in the haptoglobin type 2-2. Relative risk figures have been calculated for different phenotypes. Certain genetic combinations were found to be grossly overrepresented among the patients. The mechanisms behind the associations appear to differ. In three systems (Ss, C3 and Hp) the deviations in psoriatic patients suggest the presence of heterozygote advantage.

On the basis of immunological studies on psoriasis in recent years, it seems probable that immunological mechanisms are of importance and that psoriasis could be regarded as an immunogenetic disease. In this study, increased serum levels of an immunosuppressive factor, the pregnancy zone protein (PZ), were found in psoriatic patients. Patients with elevated levels (greater than 2 S.D. units) of PZ showed a positive association with continuous symptoms and a negative association with blood groups A and Fy(a+b-). Thus, induction of PZ occurs mainly in psoriatic patients who have a particular genetic constitution. The results support the hypothesis that PZ is not only an immunosuppressive but also an immunoreactive protein.

Seven red cell enzyme systems were examined for electrophoretic variation in a series of psoriatic patients. In two polymorphic (ADA, ES D) and four non-polymorphic systems (SOD, MDH, LDH, Dia) no deviations from normal controls were found. In the acid phosphatase system the frequency of the pa gene was found to be decreased.

In a series of 72 psoriatic patients the frequency of individuals carrying the alpha 1-AT deficiency gene Z was found to be significantly (p less than 0.001) increased.