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O Baadsgaard

Publications and source records attributed to O Baadsgaard.

At least 73 records · Page 4Linked to original sources
PubMed1990

Genotypic analysis of T-cell clones derived from cutaneous T-cell lymphoma lesions demonstrates selective growth of tumor-infiltrating lymphocytes.

The nature of T cells contained within cutaneous lesions of cutaneous T-cell lymphoma (CTCL) has not been studied at the clonal level. T cells extracted from skin lesions of two CTCL patients were cloned by limiting dilution and propagated in interleukin-2 (IL-2) containing medium with periodic lectin stimulation. Twelve T-cell clones were derived from each patient. In both cases, genotypic analysis of the T-cell clones revealed that these clones had T-cell receptor (TCR) beta- and gamma-chain gene rearrangements distinct from the predominant, presumably malignant, clone present in the skin, lymph nodes, or blood. This suggests that they were derived from presumably reactive (non-malignant) T cells. Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T-cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy.

Cell Division↗
PubMed1990

Cutaneous T-cell lymphoma lesional epidermal cells activate autologous CD4+ T lymphocytes: involvement of both CD1+OKM5+ and CD1+OKM5- antigen-presenting cells.

Cutaneous T-cell lymphoma is characterized by infiltration of the skin by activated CD4+ T lymphocytes. The mechanism by which these T lymphocytes achieve and maintain their activated state is unknown. Antigen-specific activation of T lymphocytes is dependent upon antigen-presenting cells which express HLA-DR class II major histocompatibility complex molecules, such as epidermal Langerhans cells. In addition to CD1+DR+ Langerhans cells, cutaneous T-cell lymphoma lesional epidermis contains major histocompatibility complex class II positive non-Langerhans cell populations, including CD1+OKM5+ bone-marrow-derived cells and DR+ keratinocytes. We asked whether any of these epidermal cell populations demonstrate capacity to activate T lymphocytes. Various numbers of epidermal cells from uninvolved and involved cutaneous T-cell lymphoma plaques were therefore used to stimulate autologous CD4+ and CD8+ T lymphocytes in the absence of exogenous antigen. Involved epidermal cells potently induced proliferation of CD4+ T lymphocytes (S.I. +/- SEM = 466 +/- 45). In contrast, uninvolved epidermal cells only induced background levels of proliferation (S.I. +/- SEM = 2 +/- 0.5, N = 8, p less than 0.01). Neither involved nor uninvolved epidermal cells were able directly to activate CD8+ lymphocytes. The capability of involved epidermal cells to activate CD4+ T lymphocytes was dependent upon CD1+DR+ leukocytes and not DR+ keratinocytes, because depletion of either HLA-DR+, CD1+ or HLe1+ epidermal cells totally abrogated the T-lymphocyte proliferation. Interestingly, on a cell per cell basis CD1+DR+ cells obtained from involved skin, demonstrated relative to CD1+DR+ cells from uninvolved skin, enhanced capacity to activate CD4+ T lymphocytes. Furthermore, CD1+OKM5+ cells from involved epidermis stimulated autologous CD4+ T lymphocytes. This indicates that a unique hitherto undescribed CD1+OKM5+ epidermal antigen-presenting cell population may participate in T-lymphocyte activation. These findings provide support for the concept that the epidermal cells in cutaneous T-cell lymphoma patients, particularly the antigen-presenting cells, may contribute significantly to the activation of CD4+ malignant and/or non-malignant inflammatory T lymphocytes within the skin.

Antigen-Presenting Cells↗
PubMed1990

Mechanisms of cyclosporine A inhibition of antigen-presenting activity in uninvolved and lesional psoriatic epidermis.

To elucidate how cyclosporine A affects antigen-presenting cell subsets and their function in human skin, we studied patients with psoriasis undergoing a therapeutic trial of cyclosporine A. Immunologic parameters abnormal in psoriatic epidermis were evaluated before and early in the course of therapy. We quantitated function and numbers of skin biopsy-derived epidermal cells with potential antigen-presenting cell (APC) activity. The antigen-presenting capacity of epidermal cells from normal-appearing skin to activate allogeneic T cells was profoundly inhibited (81% decrease) 7 d after the onset of therapy (p less than 0.05). Thus, cyclosporine A therapy inhibited T-cell activation mediated by Langerhans cells in uninvolved skin. By contrast, in lesional skin epidermal allo-antigen presenting activity was only partially inhibited at this early time point (55 +/- 7% decrease) (p less than 0.01, n = 8). The percentage decrease in allo-antigen-presenting cell activity correlated with reduced clinical activity of the lesions, r = 0.84. In three patients also examined at 14 d, we found an additional 42 +/- 5% decrease between day 7 and 14. Decreased allo-antigen-presenting activity in lesional skin was not associated with a decrease in the number of CD1+ Langerhans cells or epidermal cell release of detectable amounts of cyclosporine A or other soluble factors that abrogate T-cell alloreactivity. The time course and degree of inhibition of antigen-presenting capacity within involved psoriatic skin correlated best with a significant (p less than 0.01) reduction in non-Langerhans cell DR+ leukocytes (from 3.0 +/- 1.2% to 1.0 +/- 0.6% at day 7) (r = 0.71). Cyclosporine A therapy was associated with a rapid and complete loss of HLe1-DR+ keratinocytes (94% decrease at 7 d) in lesional skin despite the skin still being quite involved with psoriasis at this point and antigen-presenting cell activity being only 60% reduced. In conclusion, cyclosporine A interferes with T-cell activation by human epidermis through at least two mechanisms: 1) in uninvolved skin, rapid inhibition of Langerhans cell-mediated activation of T cells, and 2) in lesional skin, delayed inhibition of antigen-presenting activity which appears to correlate with the time course and level of reductions in non-Langerhans cell DR+ leukocytes. The antigen-presenting activity of the latter cells appears to be cyclosporine A resistant. In psoriatic lesions, early and complete loss of DR expression on lesional keratinocytes during cyclosporine A therapy is likely due to decreased lesional T-cell lymphokine production critical for keratinocyte DR expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Presenting Cells↗
PubMed1990

Phenotype, ultrastructure, and function of CD1+DR+ epidermal cells that express CD36 (OKM5) in cutaneous T-cell lymphoma.

This study investigated the phenotype and function of different antigen-presenting cells (APC) present within the epidermis of patients with cutaneous T-cell lymphoma (CTCL). Involved epidermis of CTCL compared with uninvolved was found to contain increased numbers of CD1+DR+ APC. This population was heterogeneous and comprised both leucocytes of a novel CD1+DR+CD36 (OKM5)+ phenotype and CD1+DR+CD36- indeterminate/Langerhans cells. The CD1+DR+CD36+ leucocytes did not express TcR-1, CD5, CD15, or CD22, and only a minor population expressed CD11, demonstrating that they were neither T nor B cells, and did not belong to the major CD11+ (OKM1+) blood monocyte population. Electron microscopy of purified CD36+ lesional epidermal cells (EC) demonstrated that they lacked Birbeck granules found on CD1(+)-selected Langerhans cells, and most cells exhibited features of indeterminate cells or macrophages. The capacity of EC from involved epidermis to present alloantigens was found to be increased relative to uninvolved epidermis in all patients tested, and this capacity was critically dependent upon the presence of CD45+DR+ bone marrow-derived cells but not on the presence of CD45-DR+ keratinocytes. Positive selection using MoAb against CD1 and CD36 demonstrated that both cell populations exhibited the capacity to stimulate T cells. The results indicate that a novel antigen-presenting cell population with a unique phenotype is present within involved skin of patients with mycosis fungoides. These cells express CD36 in addition to CD1 and have an ultrastructural appearance consistent with a dendritic antigen-presenting cell derivation.

Antibodies, Monoclonal↗
PubMed1990

Antigen-presenting activity of non-Langerhans epidermal cells in contact hypersensitivity reactions.

Despite the critical role of the Langerhans cells in the induction of contact hypersensitivity reactions, non-Langerhans antigen-presenting cells in already sensitized individuals may play a role in the elicitation phase of a contact hypersensitivity reaction. Following epicutaneous challenge with antigens, the number of CD1+DR+ epidermal Langerhans cells increased in a time-dependent way and, concomitantly, CD1-OKM5+DR+ epidermal non-Langerhans cells appeared. In parallel with this, the capacity of epidermal cells to present both alloantigens and auto/nominal antigens increased, and 4 days after initiation of the contact hypersensitivity reactions 33-53% of the epidermal antigen-presenting capacity was due to CD1- non-Langerhans antigen-presenting cells. Thus, contact hypersensitivity skin reactions are accompanied by the appearance of non-Langerhans antigen-presenting cells capable of presenting both alloantigens and auto/nominal antigens.

Allergens↗
PubMed1990

Abnormal function of CD4+ helper/inducer T lymphocytes in a patient with widespread human papillomavirus type 3-related infection.

Human papillomavirus-induced infections may be associated with cellular immunodeficiency. However, very little is known about the dysfunctional interactions among T lymphocytes, B lymphocytes, and antigen-presenting cells. A 30-year-old heterosexual man with a 10-year history of persistent multiple refractory flat wart lesions containing human papillomavirus type 3-related DNA sequence was studied. The patient had a severe depletion of CD4+ T lymphocytes and a compensatory increase in the number of CD8+ T lymphocytes. Impaired T-lymphocyte response to various stimuli was found. Depletion of the increased number of CD8+ T lymphocytes, which suppressed immunoglobulin production in vitro, did not restore the impaired T-lymphocyte response. Immobilized anti-CD3 beads that stimulate the T lymphocyte antigen complex in the absence of antigen-presenting cells indicated a T-lymphocyte defect, rather than a decreased antigen-presenting cell function. Thus, the pronounced cellular immunodeficiency was due to abnormal function of the CD4+ helper/inducer T lymphocytes.

Adult↗
PubMed1989

Expression and function of the UM4D4 antigen in human thymus.

UM4D4 is a newly identified T cell surface molecule, distinct from the Ag receptor and CD2, which is expressed on 25% of peripheral blood T cells, resting or activated. Monoclonal anti-UM4D4 is mitogenic for T cells and T cell clones. Since alternative activation pathways independent of Ag/MHC recognition may be important in thymic differentiation, the expression and function of UM4D4 was examined in human thymus. UM4D4 was found on the surface of 6% of thymocytes. All thymocyte subsets contained UM4D4+ cells but expression was greatest on thymocytes that were CD1- (12%), CD3+ (11%) and especially CD4-CD8- (18%). CD3+CD4- CD8- cells, most of which bear the gamma delta-receptor, were greater than or equal to 50% + for UM4D4. Moreover, anti-UM4D4 was comitogenic for thymocytes together with PMA or IL-2. Anti-UM4D4 also reacted strongly with a subset of thymic epithelial cells in both cortex and medulla. Dual color fluorescence microscopy, with anti-UM4D4 and antibodies to other thymic epithelial Ag, showed UM4D4 expression on neuroendocrine thymic epithelium but not on thymic fibrous stroma. Thus, UM4D4 is expressed on, and represents an activation pathway for, a subset of thymic T cells. In addition, this determinant, initially identified as a novel T cell activating molecule, is broadly expressed by neuroendocrine thymic epithelium. Although the function of UM4D4 on the thymic epithelial cells is not yet clear, it is possible that UM4D4 represents a pathway for the functional activation of a subset of the thymic epithelium as well as a subset of thymocytes, thus playing a dual role in T cell differentiation.

Antibodies, Monoclonal↗
PubMed1989

Rapid recovery of Langerhans cell alloreactivity, without induction of autoreactivity, after in vivo ultraviolet A, but not ultraviolet B exposure of human skin.

For therapeutic medical, cosmetic, and recreational reasons, humans expose themselves to increasing amounts of UVA. However, little is known of the photobiologic events associated with cutaneous carcinogenesis and photoaging that occur as a result of UVA exposure. UVB exposure of human skin abrogates the function of epidermal CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ non-Langerhans cell APC. This non-Langerhans cell APC population activates autoreactive immunoregulatory T cells that lead to suppressor-effector T cell function. In this report we show that, similarly to UBV, UVA exposure abrogates the function of CD1+DR+ Langerhans cells. However, in contrast to UVB, there is rapid recovery of Langerhans cell antigen-presenting cell activity and that CD1-DR+ non-Langerhans cell APC failed to appear to a significant degree. In keeping with the lack of CD1-DR+ epidermal cells, UVA exposed epidermal cells harvested 3 days after exposure functioned similarly to normal epidermis in that they activated alloreactive T cells but not autoreactive T cells in the absence of added Ag. This was in contrast to UVB irradiated epidermal cells that potently activate autoreactive T cells and contain CD1-DR+ cells. Thus, although both UVA and UVB initially depletes and inactivates CD1+DR+ Langerhans cells, the subsequent APC function of epidermal cells exposed to UVA differ profoundly from that of cells exposed to UVB. UVA radiation is less carcinogenic than UVB; differences in host responses to UV tumors may be linked to the rapid recovery of Langerhans cell function and the lack of induction of CD1-DR+ non-Langerhans cell APC after UVA exposure.

Adult↗
PubMed1989

Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome.

In mycosis fungoides the malignant T cells express lymphocyte function-associated antigen-1, which allows them to bind to epidermal keratinocytes expressing the gamma interferon-inducible intercellular adhesion molecule-1. In this report, a patient with leukemic-stage mycosis fungoides (Sézary syndrome) had widespread erythematous dermal infiltrates containing malignant T cells, but without any epidermotropism. We discovered that the T cells expressed normal amounts of functional lymphocyte function-associated antigen-1, but the keratinocytes did not express significant levels of intercellular adhesion molecule-1, which was probably due to the inability of the malignant T cells to produce gamma interferon. These results support the concept that the inability of malignant T cells to enter the epidermis may contribute to emergence of more clinically aggressive T-cell clones that are no longer confined to the skin, but infiltrate the blood, lymph nodes, and viscera, as is seen in Sézary syndrome.

Aged↗
PubMed1989

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin, but not epidermal Langerhans cells, are depleted by treatment with cyclosporin A.

Since cyclosporin A (CsA) is an immunosuppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3, 7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1+ (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1+DR+ cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1+DR+), were also reduced after CsA, epidermal non-Langerhans CD1-DR+ cells (macrophages, activated T cells, DR- keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1+DR+ Langerhans cells/non-Langerhans CD1-DR+ epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cyclosporine in dermatology.

Cyclosporine is a potent immunosuppressive agent with no appreciable effect on the bone marrow and a selective inhibitory effect on helper T cells. Oral cyclosporine was first used to prevent organ rejection but also has been reported to be effective in other disorders. In cutaneous diseases that respond to oral cyclosporine helper T cells appear to be involved in their pathogenesis. This article reviews the cutaneous diseases that have been treated with cyclosporine and its pharmacology and side effects. Two significant adverse side effects are renal dysfunction and hypertension, both of which are reversible when short-term low-dose (less than 5 mg/kg per day) oral cyclosporine is discontinued. Lymphoma is unlikely in an otherwise healthy patient who has received low-dose oral cyclosporine for limited periods. The use of oral cyclosporine in any patient should be carefully considered in terms of the risk/benefit ratio and needs to be carried out under close medical supervision. In view of the limited experience with cyclosporine in dermatology, whenever possible its use should be confined to formal clinical studies with established protocols and guidelines. Further controlled studies need to be performed to evaluate the efficacy of low-dose cyclosporine in many dermatoses and its side-effect profile, particularly over the long term.

Animals↗
PubMed1989

Psoriatic epidermal cells demonstrate increased numbers and function of non-Langerhans antigen-presenting cells.

The recent findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raises the possibility that cellular immune processes play a major role in the pathogenesis of psoriasis. We therefore investigated the phenotype and function of cells within psoriatic epidermis that can play a role in cellular immunologic reactivity. Double fluorescence microscopic studies with monoclonal antibodies of epidermal cells in suspension (EC) and of histologic sections demonstrated that involved psoriatic skin contained a significantly increased number of non-Langerhans cell T6-DR+ EC (4.9 + 2.1%) relative to uninvolved (0.3 +/- 0.1%), p less than 0.01. This non-Langerhans cell population was comprised of DR+ monocytes, DR+ activated T lymphocytes, a few DR+RFD1+ antigen-presenting cells (APC), and DR+ keratinocytes. Langerhans cell (LC) levels in EC suspension were not different between involved and uninvolved psoriatic epidermis. Functional studies demonstrated that involved psoriatic epidermal cells had an increased capacity to induce T-cell activation and proliferation relative to uninvolved EC (p less than 0.04). This increased APC activity was due to the non-LC T6-DR+HLe1+ APC population and not to DR+ keratinocytes. These results demonstrate that involved psoriatic epidermal cells contain both an increased number and function of antigen-presenting cells. The pathogenetic mechanisms in psoriasis may be related to ongoing cellular immune responses in the skin, and the effect of CsA may be mediated through a suppressive effect on the enhanced antigen-presenting cell activity.

Antigen-Presenting Cells↗
PubMed1989

Decreased number and function of antigen-presenting cells in the skin following application of irritant agents: relevance for skin cancer?

The mechanism of irritant dermatitis and the immunologic consequences of such reactions are unclear. We evaluated the number and function of epidermal antigen-presenting cells contained in epidermal cell suspensions obtained from normal and irritant patch test reaction sites. Application of sodium lauryl sulfate or croton oil to human skin in vivo resulted in a progressive depletion in the number of epidermal OKT6+HLA-DR+ (T6+DR+) Langerhans cells (LC) from 3.1 +/- 0.2% of total epidermal cells (EC) to 1.2 +/- 0.1% after 8 d (mean values +/- SEM, N = 9). Between 1-4 d irritant patch test sites demonstrated an influx of non-Langerhans cell T6-DR+ cells. These cells were not DR+ keratinocytes but appeared to be of bone marrow derivation because they expressed the marker, HLe1. Among bone marrow derived cells, the T6-DR+EC appeared to be of monocyte, macrophage lineage, because they expressed the determinant recognized by the OKM5 (M5) antibody. Despite the induction of M5+DR+EC the total number of DR+EC showed progressively decreasing percentages over an 8-d period. Partial recovery to 73 +/- 12% of control value was observed at 2 weeks, with full recovery by 4 weeks after challenge. Concomitantly with the depletion of DR+EC, the capacity of EC to present alloantigens to T cells decreased. This reduction in antigen-presenting cell activity was strongly correlated to the reduction in total DR+ EC (r = 0.94, p less than 0.05). Thus, the capacity of irritants such as croton oil to abrogate the function of epidermal antigen-presenting cells may be related to the tumor promoting potential of these agents.

Administration, Cutaneous↗
PubMed1988

Human epidermal cells from ultraviolet light-exposed skin preferentially activate autoreactive CD4+2H4+ suppressor-inducer lymphocytes and CD8+ suppressor/cytotoxic lymphocytes.

In vivo exposure of human epidermis to UV abrogates the function of T6+DR+ Langerhans cells and induces the appearance of Ag-presenting T6-DR+ OKM5+ cells in the epidermis. Since UV exposure of murine skin results in Ts lymphocyte activation, we investigated the capacity of human epidermal cells (EC) harvested 3 days after in vivo UV exposure to activate regulatory and effector autologous T lymphocyte subsets. T lymphocytes were separated into CD8+ suppressor/cytotoxic lymphocytes and CD4+ helper/inducer lymphocytes by C lysis and panning. The CD4+ subset was further divided by using the 2H4 mAB to obtain CD4+2H4+ lymphocytes (inducers of TS lymphocytes) and CD4+2H4- lymphocytes (inducers of B cell Ig production and inducers of cytotoxic T cells). Unirradiated suction blister-derived EC from control skin (C-EC) and from skin exposed in vivo to UV (UV-EC) were cultured with purified autologous T lymphocyte subsets in the absence of added Ag. The resultant T lymphocyte proliferation was detected by [3H]thymidine uptake. UV-EC were highly effective in the stimulation of CD4+ lymphocytes, whereas C-EC were poor stimulators. The stimulator effect of UV-EC was abrogated after depletion of DR+ UV-EC. When CD4+ lymphocytes were fractionated, UV-EC consistently demonstrated enhanced ability to stimulate suppressor-inducer CD4+2H4+ lymphocytes relative to C-EC. Although less responsive than CD4+2H4+ lymphocytes, CD4+2H4- lymphocytes also demonstrated greater proliferation to UV-EC than to C-EC. Neither UV-EC nor C-EC were able to activate CD8+ lymphocytes devoid of CD4+ lymphocytes. However, after addition of rIL-2 at concentrations that allow binding only to the high affinity IL-2R on T lymphocytes, UV-EC induced vigorous proliferation of CD8+ lymphocytes, whereas C-EC induced only background levels of proliferation. C lysis of leukocytes resident within UV-EC resulted in 66 to 70% reduction of CD8+ lymphocyte proliferation. In conclusion, UV-EC may activate CD8+ lymphocytes by at least two pathways: (1) UV-EC activation of CD4+2H4+ lymphocytes may induce differentiation/proliferation of CD8+ suppressor cells and (2) UV-EC activation of CD4+ cells may induce IL-2 production, that, in combination with UV-induced epidermal leukocytes, stimulates CD8+ cells.

Adult↗
PubMed1988

Expression of OKM5 antigen on epidermal cells in mycosis fungoides plaque stage.

To characterize and quantitate potential antigen-presenting cell subsets in the epidermis of patients with cutaneous T-cell lymphoma, epidermal cells in suspension were obtained from involved and uninvolved skin. Involved epidermis contained increased numbers of OKT6+HLA-DR+ Langerhans cells and a variable number of OKM5+ epidermal cells (ECs) in all mycosis fungoides (MF) patients tested (N = 14). The OKM5+ EC population from involved epidermis of MF patients were heterogeneous and comprised both OKM5+HLe1- keratinocytes and OKM5+HLe1+ leukocytes. Uninvolved epidermis, in 6 of 14 patients with MF, contained a small number of OKM5+ leukocytes; however, no OKM5+ keratinocytes were detected. Neither OKM5+ leukocytes nor OKM5+ keratinocytes were detected in the epidermis obtained from healthy controls. The increased number of potential antigen-presenting cells, that is, OKT6+HLA-DR+ Langerhans cells and OKM5+HLA-DR+ monocytic leukocytes, in the epidermis of patients with MF may be important for the activation of abnormal T cells contained within the epidermis of these patients. Such activated T cells may release gamma-interferon and induce expression of both HLA-DR and OKM5 antigens on keratinocytes. OKM5+ keratinocytes are present in the epidermis of patients with MF, but not in normal skin, and may thus play a role in the pathogenetic mechanisms of mycosis fungoides by recruitment of immunocompetent cells to the epidermis.

Aged↗
PubMed1988

Increased urinary excretion of 1.4-methyl-imidazoleacetic acid in patients with atopic dermatitis.

To investigate whether the overall histamine turnover is increased in patients with atopic dermatitis, without respiratory disease, the urinary excretion of the main histamine metabolite 1.4-methyl-imidazoleacetic acid (MIAA) was examined in 23 patients and in 23 age- and sex-matched non-atopic controls. The patients excreted significantly more MIAA than the controls. One third of the patients however, showed MIAA excretion within or below normal range. The MIAA excretion was neither correlated to the severity of the eczema nor to the total serum IgE. It was concluded that histamine does not play a significant role in the pathophysiology of atopic dermatitis, and that the great variation in MIAA excretion, and hence the histamine turnover, reflected the spectrum of histamine releasability in the patients.

Adolescent↗