V. Bottari

Psoriasis: comparison of immunological markers in patients with acute and remission phase

The immune system involvement in psoriasis has been documented by the presence of activated T-cells both in peripheral blood and in psoriatic skin lesions and by the intervention of cytokines in the inflammatory process. On this basis, we have undertaken a study in order to examine, in addition to activation markers such as CD25 and CD54 (ICAM-1) on peripheral blood mononuclear cells (PBMNCs) surface, serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), soluble ICAM-1 (sICAM-1), soluble CD4 (sCD4), soluble CD8 (sCD8), beta 2-microglobulin and fibronectin (FN) in psoriatic patients analyzed both in acute and remission phase obtained by topical therapy alone. Our results show that PBMNCs expressing IL-2 receptor (CD25) were increased both in percentage and absolute number in respect to controls, and were not modified after remission. On the contrary, the significantly higher number of CD54+ lymphocytes evaluated in acute psoriasis, showed a reduction during the remission phase, even if the values persisted higher than controls. Serum levels of sIL-2R, sICAM-1, sCD4, sCD8 and beta 2-microglobulin were significantly higher than controls both in acute and remission phase; only FN levels were found to be lower, in patients evaluated both in acute psoriasis and after therapy, in respect to normal donors. On the whole, these results seem to indicate the persistence of both cellular and soluble activation markers even in psoriasis remission phase; in this light, we can suppose that topical therapy alone is not able to efficiently down-regulate activation mechanisms involved in the pathogenesis of the disease.

Cyclosporin A (CyA) reduces sCD30 serum levels in atopic dermatitis: a possible new immune intervention

Atopic dermatitis (AD) is a chronic inflammatory skin disease frequently associated with asthma, rhinitis, and food allergy. Lymphocytes producing Th2‐type cytokines (such as interleukin [IL]‐3, IL‐4, and IL‐5) have been thought to have a key role in the pathogenesis of the disease. We have recently demonstrated that elevated serum levels of the soluble form of CD30 (sCD30), an activation marker of Th2‐cell clones, correlates with disease activity in pediatric patients suffering from AD. Clinical trials have demonstrated that cyclosporin A (CyA) treatment resulted in significant improvement of clinical symptoms in patients affected with AD. In this study, we evaluated the role of CyA in modulating sCD30 release in a group of adult patients affected by severe AD treated with CyA at the dosage of 3.5 mg/kg body weight for 12 weeks. Our results demonstrated, in parallel with an improvement of clinical symptoms, a significant reduction of serum levels of both IL‐4 and sCD30, thus suggesting that CyA can prevent the activation of Th2 cells observed in AD.

Surface markers and cytotoxic activities of lymphocytes in monoclonal gammopathy of undetermined significance and untreated multiple myeloma

SummaryTo determine whether monoclonal gammopathy of undetermined significance (MGUS) resembles multiple myeloma (MM) with regard to phenotype and functional activity, 16 patients with MGUS and 16 with untreated MM were studied for surface markers and cytotoxic activities phytohemagglutinin-induced cellular cytotoxicity (PHA-ICC), antibody-dependent cellular cytotoxicity, natural killer (NK) activity. Our data showed a consistent immunological similarity between the two diseases. An increase in OKT8+ cells was evident in both patient groups and a significant reduction in the T4/T8 ratio, more pronunced in MM, was observed. Alterations in NK activity or ADCC were not found in MGUS or MM. A significant increase in PHA-ICC was demonstrated in the two diseases. The increase in PHA-ICC observed seems to be attributable to an increased frequency and/or lytic efficiency of PHA-ICC lymphoid effector cells. These data suggest that similar immunological alterations are common to the two diseases. The greater helper/suppressor ratio reduction observed in MM seems to be related to the more severe clonal proliferation in these patients.

PHA-ICC, ADCC and NK in patients with ANLL in CR: Human fibroblastic interferon fails to increase NK-active cell frequency

PHA-ICC, ADCC and NK activity of PBL were studied in ten patients with ANLL in CR and in eighteen normal controls in the presence and absence of HFIF. No statistically significant differences were recorded among the two groups with regard to basic lymphocyte functions. Although the parameters of lymphocyte function remained analogous for those tested, the analysis at the single cell level revealed that HFIF stimulation increases the number of NK active cells and target binding cells among normals, but not in leukemic patients.

Ability of recombinant interferon γ in vitro to restore the defective polymorphonuclear-cell-but not lymphocyte-mediated cytotoxic activities in patients with myelodysplastic syndromes

SummaryIn this study we analysed the in vitro effect of recombinant interferon γ on cytotoxic activities mediated by both lymphoid and polymorphonuclear cells from 16 patients with myelodysplastic syndromes. Our results indicate the inability of interferon to restore the defective natural killer activity, natural killer cells and lectin-induced cytotoxicity. On the contrary we detected a boosting effect on the depressed polymorphonuclear cell cytotoxic activities. In our view, the ability of interferon to potentiate polymorphonuclear cell lytic efficiency could support an alternative defensive pathway against either neoplastic or infectious agents.

Motility and oxidative metabolism of normal polymorphonuclear leukocytes in acute non-lymphoid leukemia in complete remission

SummaryPolymorphonuclear leukocytes (PMN) from 11 patients with acute non-lymphoid leukemia (ANLL) in complete remission and off therapy for at least 22 months were studied for their oxidative metabolism and motility. In all patients, PMN motility tests revealed no consistent abnormality, whereas cells from 2 patients showed a selective impairment of oxidative metabolism, as assessed by the low capacity to reduce nitroblue tetrazolium and/or to generate chemiluminescence when stimulated with phorbol myristate acetate. No morphological change was detectable in PMN from these patients. However, the functional alterations appeared related to an early tendency to relapse, as both patients developed an acute phase after 5 and 9 months from testing, respectively. This suggests that abnormal PMN may circulate in ANLL patients in complete remission in spite of a normal differential count and that functional studies may be useful for detecting such a population.

Childhood Abnormal Expansion of Large Granular Lymphocytes

An expansion of large granular lymphocytes (LGL) in the peripheral blood (PB) of a 10-year-old child is described. After a long history of uncertain hematological diagnosis and chemotherapeutic regimens and 2 years after any kind of therapy, the child showed in PB an expansion of LGL E-rosette+, OKT3+, OKT8+, Leu7+. Cytotoxic activities showed high natural killer activity and an increase of PHA-induced cytotoxicity. Histological findings in the spleen, abdominal lymph nodes and bone marrow excluded a lymphoproliferative disease, but liver biopsy revealed a chronic aggressive hepatitis.

Squamous Cell Carcinoma Related Antigen (SCC-rAg), sICAM-1 and β 2Microglobulin are Usefull Markers of Disease Activity in Psoriasis

genes involved in glycide metabolism and a glucose transporter are located in this genomic area. Moreover, recent data suggest that Rh is also a transporter. ACPl is a highly polymorphic phosphotyrosine phosphatase (PTPase): it is composed by two distinct isoforms F and S and may have an important role in the modulation of the postreceptorial pathway of insulin action. The association of the two clusters with different ACPl isoforms represents a strong indication ofbiochemical heterogeneity ofneuropathic complications. In fact, F and S isoforms show different structure and biochemical properties and have probably different functions. On the other hand the association with RhE may represent the effect of complex haplotypes of genes located in the short arm of chromosome 1 involving glucose transport and metabolism.

Raynaud's Phenomenon: Immunological Aspects

The isolated Raynauds Phenomenon (RP) associated with an abnormal nailfold capillary microscopy, and/or detectable antinuclear factors is considered a risk factor for Connective Tissue Diseases (CTDs), and rnay precede the overt disease (in particular Systemic Sclerosis, SSc) for several years. This clinical picture could be classified as ealy secondary or suspected RP, and its predictive significance is still under investigation, being not clarified the pathogenetic mechanism underlying the progression from early symptoms to a major CTD. In this light, the appearance of circulating autoantibodies, their prevalence and/or association with peculiar clinical findings are commonly considered the steps of the immunopathological damage progression. More recent data, concerning the role of some cytokines in CTD, suggest the hypothesis that an altered cytokine network could be also involved in the early events that lead, via fibroblast and endothelial cell injury, to connective tissue damage. In this light, the involvement of endothelium and perivascular connective tissue, commonly observed in RP patients, could be mediated via cytokine-driven activation and adhesive mechanisms. Furthermore, from the inflammed microvascular environment both activated immune cells and soluble factors, spreading to the bloodstream, could share in determining the chronic immunoflogosis, the following fibrotic evolution, and the multiorgan involvement. By considering this hypothesis, we analyzed serum levels of some proinflammatory and immunomodulating cytokines (i.e. IL-l b, TNF-a, IL-6), and soluble receptors for IL-2 and TNF-a in patients affected by isolated RP, classified as primary and early secondary, in comparison to control groups: both normals and Scleroderma patients. Our preliminary data suggest that high levels of proinflammatory cytokines are present in all patients groups, while sIL-2R is released in significantly higher amounts only in CTD patients. Interestingly, sTNF-R type II serum levels characterize the difference between primary and early secondary RP, and this datum suggests that other parameters than autoantibodies could be assessed in patients suspected for a clinical progression to CTD.

Hereditary Angioneurotic Edema

Hereditary angioedema results from a congenital deficiency offunctional C1 inhibitor and is characterized by episodic bouts of edema of the extremities, face, trunk, airways or abdominal viscera, apparently arising either spontaneusly or following stress and/or trauma. Cutaneous edema is non pitting and non pruritic, laryngeal is often life-threatening, abdominal is almost always painful. The role of trauma in the aetiopathogenesis of HANE is linked to the close relationships existing between C and multi-enzyme systems in the plasma, particularly the coagulation cascade. The mechanism(s) of action involved in the case of mental stress causing acrisis is unclear, however some possible links between neuroendocrine system and HANE have been studied and reported: high plasma BE concentrations have been found by us during HANE attacks as well as during symptom free periods together (in women) with a very high prevalence ofPCO and ofMFO that are linked to hypothalamic-pituitary disfunction. Of all possible mucosal sites, the most life-threatening situation is represented by laryngeal edema which, in the absence of i.v. injection of ClINH concentrate, often requires emergency tracheostomy. Warning signs of glottis involvement are changes in voice timbre or dysphagia. Severe dyspnea and signs of acute respiratory distress are also characteristic during an attack. On the other hand, the incidence of abdominal pain is greater, with frequent bouts of colic, nausea, vomiting and diarrhea. These cases must necessarily be differentiated from acute abdominal crises of surgical interest and vice versa. One of the mainstays in long term management of HANE is the long term therapy with danazol, a mild androgen capable of correcting low C lINH concentrations and of almost completely put into remission the typical symptoms of the disease. Along with such treatment, HANE clinical symptoms consistently improve, as well as C IINH serum concentrations increase. Recently, the use of LH-RH agonist leuprolide acetate is suggested by our group in long term treatment of women affected with HANE. The patients studied showed striking improvements of clinical symptoms of the disease, especially for abdominal pain.