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Biomedical subjects

Kristin M Leiferman

Publications and source records attributed to Kristin M Leiferman.

12 recordsLinked to original sources
PubMed2006

Identification of basophils by a mAb directed against pro-major basic protein 1.

BACKGROUND: Basophils possess characteristics of both mast cells and eosinophils, and all 3 cell types often are found together, particularly during allergic reactions. A mAb (J175-7D4) generated against the recombinant pro-form of human eosinophil granule major basic protein 1 (rproMBP1) appeared to stain only basophils in tissue specimens. OBJECTIVE: We investigated J175-7D4 to characterize its specificity for basophils. METHODS: Fluid-phase immunoprecipitation, Western blotting, and immunocytochemistry and immunohistochemistry were used to establish the specificity of J175-7D4. RESULTS: First, J175-7D4 binds to various glycosylated and proteolytically processed forms of rproMBP1, but not to major basic protein. Second, cells transfected with the rproMBP1 gene and human placental tissue (known to express the pro-form of major basic protein 1 [proMBP1]) stain specifically with J175-7D4. In contrast, although mature eosinophils contain substantial major basic protein, they lack proMBP1 and do not stain. Neutrophils, lymphocytes, monocytes, and skin mast cells also are not stained. However, blood basophils are stained by J175-7D4, anti-IgE, Wright-Giemsa (metachromatically), and a previously characterized basophil-specific mAb, 2D7. Finally, formaldehyde-fixed, paraffin-embedded basophils are identically detected by J175-7D4 and 2D7, and J175-7D4 also recognizes putative basophils in formaldehyde-fixed, paraffin-embedded tissue specimens from inflammatory dermatoses, such as atopic dermatitis and delayed pressure urticaria. CONCLUSION: The J175-7D4 mAb recognizes proMBP1 as a novel marker for human basophils. J175-7D4 should prove useful for characterizing basophil involvement in human health and disease.

Antibodies, Monoclonal↗
PubMed2006

Dermatitis herpetiformis and partial IgA deficiency.

Although the specific IgA autoantibody responsible for the pathogenesis of dermatitis herpetiformis (DH) is unknown, the presence of IgA is considered essential in the pathogenesis of DH. To date, no cases of IgA deficiency have been reported in DH. In contrast, IgA deficiency is found in 2% to 3% of patients with celiac disease, a rate 10 to 15 times higher than the normal population. We report 2 patients with DH who also have partial IgA deficiency. We evaluated the sera of these patients for the presence of IgA autoantibodies to endomysium, tissue transglutaminase, epidermal transglutaminase, and gliadin. Both patients were found to have IgA endomysial and tissue transglutaminase antibodies, and serologic markers for DH. Corresponding IgG autoantibodies were not useful serologic markers of DH in the setting of IgA deficiency, as they often are in celiac disease. We then screened 98 DH sera for total IgA levels and identified 1 additional case with IgA deficiency. In conclusion, DH may develop in patients with partial IgA deficiency, indicating that pathogenically directed IgA antibodies are likely sufficient for cutaneous IgA deposition in this disease.

Adult↗
PubMed2006

Neonatal eosinophilic pustulosis.

A pre-term, 7-week-old male infant presented with a recurrent pustular eruption involving his face and scalp with associated peripheral blood eosinophilia. Skin biopsy revealed spongiosis with numerous dermal and epidermal eosinophils without predominant follicular involvement. Immunohistology showed deposition of eosinophil granule major basic protein and eosinophil derived neurotoxin in the dermis and epidermis. He responded to conservative management. We discuss the differential diagnosis of neonatal eosinophilic pustular eruptions and suggest the term 'neonatal eosinophilic pustulosis' to best describe our case.

Anti-Bacterial Agents↗
PubMed2005

The hypereosinophilic syndromes: still more heterogeneity.

In 1968, the term hypereosinophilic syndromes (HES) was coined to refer to a spectrum of eosinophil-associated diseases presumed to be caused by an underlying immunological pathology. In the 1990s, the identification of an HES subset with T lymphocyte clonality and production of cytokines, particularly IL-5, validated this concept. Then, in 2002, imatinib mesylate, which was introduced for the treatment of chronic myelogenous leukemia, effectively controlled another subgroup of HES patients. Imatinib's target is a novel constitutively-active kinase. Most imatinib-responsive HES patients show an increased number of bone marrow mast cells and elevated serum tryptase; mast cells, lymphocytes and neutrophils express the novel kinase. This new information critically modifies our view of HES and indicates that several cell lines are altered and likely to contribute to HES pathophysiology.

Benzamides↗
PubMed2004

Dermatologic drug reactions.

Cutaneous drug reactions have a variety of clinical presentations. This review focuses on the most common or severe cutaneous reaction patterns. Knowledge of the clinical morphology and the most commonly associated medication aids in rapid diagnosis and institution of the appropriate therapy.

Diagnosis, Differential↗
PubMed2004

Hypereosinophilic syndrome: case presentation and update.

Persistent peripheral blood eosinophilia can be associated with a variety of diseases, ranging from parasitic infection to gastrointestinal disease to vasculitis to the hypereosinophilic syndrome (HES). Mucosal ulcerations are a variant presentation of the HES that appear to be markers for a mutation that characterizes a subgroup of patients with HES responsive to treatment with imatinib mesylate. We present a patient with peripheral blood eosinophilia and severe recurrent mucosal ulcers and discuss his presentation in the context of new information about the evaluation, disease progression, and treatment of HES.

Adult↗
PubMed2003

Interactions of eosinophil granule proteins with skin: limits of detection, persistence, and vasopermeabilization.

BACKGROUND: Eosinophil granule proteins, including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and major basic protein (MBP), are prominently deposited in skin in several cutaneous disorders and likely contribute to disease pathology. OBJECTIVE: We sought to determine the limit of detection, persistence, and vasopermeabilization activity of the eosinophil granule proteins in skin. METHODS: The eosinophil granule proteins were injected intradermally. Their minimum detectable concentrations in human surgical waste skin and their persistence in guinea pig skin were determined by indirect immunofluorescence. Vasopermeabilization activity in the guinea pig without and with H1 antihistamine (pyrilamine maleate) pretreatment was assessed by extrusion of Evans blue dye-treated plasma. RESULTS: The lowest detectable cutaneous concentrations were 0.05 micromol/L EPO, 0.1 micromol/L MBP, 0.25 micromol/L ECP, and 1 micromol/L EDN. Granule proteins persisted in guinea pig skin in vivo for 1 week (EPO), 2 weeks (ECP), 2.5 weeks (EDN), and 6 weeks (MBP). Each of the eosinophil granule proteins increased cutaneous vasopermeability in a concentration-dependent manner. The potency of vasopermeabilization induced by each granule protein was comparable with that of histamine. Pyrilamine maleate pretreatment of guinea pigs did not alter increased vasopermeability induced by ECP and EDN but significantly inhibited that induced by EPO and MBP. CONCLUSIONS: Micromolar concentrations of eosinophil granule proteins are often deposited in skin in eosinophil-associated cutaneous disorders such as atopic dermatitis. These pathophysiologically relevant concentrations of eosinophil granule proteins cause increased cutaneous vasopermeability (both by means of histamine-independent and histamine-dependent mechanisms) and might alter cutaneous function for days to weeks.

Animals↗
PubMed2003

Localization and regulation of pregnancy-associated plasma protein a expression in healing human skin.

Pregnancy-associated plasma protein A (PAPP-A) is an IGF-binding protein-4 (IGFBP-4) metalloproteinase that cleaves inhibitory IGFBP-4 to amplify local IGF-I bioavailability in vitro. Thus it has functional implications in injury/repair responses. In this study we determined PAPP-A expression in healing human skin. Wounds were induced with a scalpel on the forearms of three normal subjects and were allowed to heal by first intention. Biopsies obtained on d 0, 2, 8, and 14 were processed for immunohistochemical detection of PAPP-A, IGF-I, and IGFBP-4. In uninjured skin (d 0), strong staining for PAPP-A was present in the epidermis, sweat and sebaceous gland epithelial cells, hair follicles, and blood vessels; no PAPP-A was detected in dermal fibroblasts or with mature collagen bundles. IGF-I localized strongly to epithelial cells of skin glands was weak to moderate in epidermis and blood vessels, and was absent in dermal cells. Weak focal staining for IGFBP-4 was found within uninjured epidermis. During wound healing, PAPP-A expression was induced in dermal granulation tissue within and adjacent to the injury. PAPP-A was present in dermis on d 2 and was increased in intensity and extent on d 8 and 14. PAPP-A expression also increased in the epidermis. PAPP-A expression in cells of granulation tissue colocalized with alpha-smooth actin staining of myofibroblasts and new blood vessels as well as with CD68 staining of macrophages and was associated with the compact, newly synthesized collagen of the healing wound. IGF-I staining was enhanced in the epidermis localized to the area of the incision and in granulation tissue associated with lymphoid cells. IGFBP-4 staining of the epidermis remained unchanged during wound healing, but was induced in the fibroblastic cells of granulation tissue over time. These data demonstrate localized and regulated expression of PAPP-A in human skin and suggest that PAPP-A may play an important role in an integrated IGF system in wound healing and tissue remodeling in vivo.

Actins↗
PubMed2002

Treatment of hypereosinophilic syndrome with imatinib mesilate.

Patients with hypereosinophilic syndrome show persistent eosinophilia without recognised cause. We treated five such patients with 100 mg imatinib mesilate (formerly STI-571) daily; four male patients with normal serum interleukin 5 showed complete haematological responses; a female patient who did not respond had raised serum interleukin-5 concentrations. One patient developed leucopenia after 4 days of treatment; counts returned to normal when treatment was stopped. After 1 month, eosinophilia recurred; with further treatment for 2 days, eosinophil counts again became normal. All patients who responded stopped other treatments and reduced imatinib mesilate to 200 mg per week. This drug effectively controls eosinophilia in patients with hypereosinophilic syndrome and normal interleukin-5 concentrations.

Administration, Oral↗
PubMed2002

Evidence for pathogenic involvementof eosinophils and neutrophilsin Churg-Strauss syndrome.

BACKGROUND: Churg-Strauss syndrome (CSS) is a multi-organ disease with tissue and blood eosinophilia. OBJECTIVE: Our aim was to study eosinophil and neutrophil involvement in CSS. METHODS: Eight lesional skin biopsy specimens from 6 patients with CSS and serum and blister fluid from one patient were tested for eosinophil and neutrophil activity. Indirect immunofluorescence on skin specimens used antibodies to eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase (NE). Serum and blister fluid specimens were analyzed for granule protein levels and for eosinophil-activating cytokines. RESULTS: Indirect immunofluorescence showed prominent cellular and extracellular staining for EDN in skin biopsy specimens; MBP staining was less extensive. Five biopsy specimens showed marked cellular NE staining; 4 showed prominent extracellular NE. Serum and blister fluid specimens contained elevated MBP, EDN, and interleukin 5 levels and enhanced eosinophil survival in culture. Granulocyte-macrophage colony-stimulating factor and interleukin 5 were detected in blister fluid. Blister fluid contained more NE than normal serum. CONCLUSIONS: Both eosinophils and neutrophils likely participate in skin lesion development in CSS.

Adult↗
PubMed2002

Diagnostic features of pemphigus vulgaris in patients with bullous pemphigoid. Molecular analysis of autoantibody profile.

BACKGROUND: The simultaneous presence of features of pemphigus vulgaris (PV) in patients with bullous pemphigoid (BP) has previously been reported in the literature. OBJECTIVE: The purpose of this retrospective study is to present 13 patients with an initial diagnosis of BP, who subsequently demonstrated coexistent serological features of both BP and PV. METHODS: The following information on each patient was documented, at the time of initial diagnosis: clinical profile on presentation, histology, direct immunofluorescence, indirect immunofluorescence (IIF) using monkey esophagus as substrate, salt-split skin (SSS) and an immunoblot assay. Since all 13 patients failed to respond to conventional systemic therapy, intravenous immunoglobulin (IVIg) was used as an alternative treatment modality. Prior to initiating IVIg therapy, in all 13 patients, serological studies were performed. In addition to IIF using monkey esophagus, an immunoblot assay and SSS, an enzyme-linked immunosorbent assay (ELISA) was performed to detect antibodies to desmogleins. These different assays were done to identify pathological autoantibodies typical of BP and PV. A control group of 25 healthy normal individuals, 37 patients with BP, 17 patients with PV and 12 patients with pemphigus foliaceus were used for comparison of serological studies. RESULTS: At the time of initial presentation, histological and immunopathological studies confirmed the diagnosis of BP in all 13 patients. Prior to the initiation of IVIg therapy, results of IIF using monkey esophagus as substrate demonstrated high levels of anti-intercellular cement substance (anti-ICS) or antikeratinocyte cell surface antibody. Sera of all 13 patients on SSS bound to the epidermal side of the split. In an immunoblot, using bovine gingival lysate as substrate, sera of 6 patients bound to both a 230-kD (BP Ag1) and 180-kD protein (BP Ag2), while 7 sera bound to only a 230-kD protein. All 13 patients had high levels of antibodies to desmoglein 3 on ELISA. In a pilot experiment, the anti-ICS antibody in sera from 6 random patients was found to be predominantly of the IgG4 subclass. Use of IVIg resulted in an effective clinical response and the maintenance of a prolonged clinical remission. CONCLUSION: In patients with BP, who are nonresponsive to conventional therapy, the presence of two autoimmune diseases or a dual diagnosis should be considered.

Aged↗