[The foreign particles injection induces stable hyaline cells differentiation in the hemolymph of the blowfly Calliphora vicina larvae].

The stable hyaline cells (thrombocytoids precursors) are prevailing haemocytes type in young larvae of Calliphora vicina. Their concentration decreased significantly during the crop emptying and became completely absent in wandering larvae. However, the injection of foreign particles into the haemocoel induced evident increase in the number of stable hyaline cells by means of transformation from prohaemocytes within 24 h after the treatment. Maximum of hyaline cells concentration is achieved on the 2-3 day when the part of them starts to transform into prothrombocytoids. Injection of both abiotic (charcoal) and biotic (human erythrocytes) foreign particles exerts an identical effect. Puncture of the body wall, bacterial immunization and injection of saline did not induce hyaline cells appearance. In crop emptying larvae, the stable hyaline cells originate within the clusters of undifferentiated steam cells, i. e. prohaemocytes. After the completion of crop emptying in wandering and diapausing larvae, preliminary dedifferentiation of very young plasmatocytes may be also observed. It is suggested that specification of the stable hyaline cells is induced by thrombocytoids after engulfing of the injected foreign particles and forming of their agglutinates.

[Differentiation of the stable hyaline cells in response to foreign particles injections into the larvae of blowfly calliphora vomitoria].

Injection of foreign particles (charcoal and human erythrocytes) into the larvae of Calliphora vomitoria provokes the complex immune response including their phagocytosis, nodulation and encapsulation by plasmatocytes and thrombocytoids. Precursors of thrombocytoids and analogs of Drosophila lamellocytes are very frequent during the periods of feeding and crop emptying, but fully disappear in wandering larvae. Injection of charcoal or erythrocytes into crop emptying larvae leads also to a dramatic increase in the number of stable hyaline cells, precursors of thrombocytoids. The hyaline cells differentiate from prohaemocytes and, quite possibly, from young weakly-specialized plasmatocytes in a day after injection. Later they are transformed to prothrombocytoids and thrombocytoids. The number of hyaline cells and young plasmatocytes in the crop emptying larvae of C. vomitoria is far greater than that in the same age larvae of C. vicina. Presumably it accounts for significantly increasing rate of stable hyaline cells differentiation in the injected larvae of C. vomitoria. Their part after injection of charcoal particles or erythrocytes may reach 40-50 % of the main haemocyte number compared to 20-25% in C. vicina. After completion of the crop emptying, the rate of hyaline cells differentiation in response to the foreign particles injection is evidently reduced but remains to be distinctly visible. Injections of saline also stimulate the differentiation of the stable hyaline cells from prohaemocytes but elevation of their amount is more weak and gradual. The bacterial immunization and needle prick show no effect. The treatments, inducing the rising of hyaline cells differentiation, lead also to pupariation delay. This correlation suggests involvement of the endocrine system into this process.

Hyalin is a cell adhesion molecule involved in mediating archenteron-blastocoel roof attachment.

The US National Institutes of Health has designated the sea urchin embryo as a model organism because around 25 discoveries in this system have led to insights into the physiology of higher organisms, including humans. Hyalin is a large glycoprotein in the hyaline layer of sea urchin embryos that functions to maintain general adhesive relationships in the developing embryo. It consists of the hyalin repeat domain that has been identified in organisms as diverse as bacteria, worms, flies, mice, sea urchins and humans. Here we show, using a polyclonal antibody raised against the 11.6 S species of hyalin, that it localizes at the tip of the archenteron and on the roof of the blastocoel exactly where these two structures bond in an adhesive interaction that has been of interest for over a century. In addition, the antibody blocks the interaction between the archenteron tip and blastocoel roof. These results, in addition to other recent findings from this laboratory that will be discussed, suggest that hyalin is involved in mediating this cellular interaction. This is the first demonstration that suggests that hyalin functions as a cell adhesion molecule in many organisms, including humans.

Cell membrane reactivity of MIB-1 antibody to Ki67 in human tumors: fact or artifact?

Ki67 immunohistochemistry is a widely used marker of the tumor proliferative fraction. Apart from the nuclear staining of dividing cells, MIB-1 monoclonal antibody was also found to stain the cell membrane of some tumor types. Indeed, such membrane reactivity was proposed as a diagnostic feature of hyalinizing trabecular tumor (HTT) of the thyroid. To verify the diagnostic role of Ki67 membrane pattern, 6 HTTs, 8 pulmonary sclerosing hemangiomas (SH), and 6 other human tumors with MIB-1 cell membrane immunoreactivity were stained by immunoperoxidase with 5 different anti-Ki67 antibodies in different experimental conditions. We show here that the cell membrane reactivity reported in HTT is produced only by MIB-1 and not by other antibodies to Ki67 (including commercially available mouse and rabbit monoclonal antibodies). In addition, this peculiar pattern is obtained only if the reaction is performed at room temperature, because automated immunostainers which operate at 37 degrees C do not produce any MIB-1 membrane localization. The same findings were obtained in the other 6 tumors. Conversely, sclerosing hemangioma of the lung did not produce any MIB-1 cell membrane reactivity in our hands. A cross-reactivity of the MIB-1 monoclonal antibody with an epitope expressed at the cell membrane level (rather than an artifact) seems the most likely explanation for this finding, because the immunoreactivity is generally intense and uniform in the membrane positive tumors. We conclude that when Ki67 immunohistochemistry is used for diagnostic purposes in a suspected HTT, only MIB-1 clone at room temperature should be employed.

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage.

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (alpha-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65% +/- 3.24%), while extrapulmonary diffuse alveolar damage (9.52% +/- 3.64%) and idiopathic diffuse alveolar damage (7.34% +/- 2.11%) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36% +/- 3.12%), extrapulmonary (16.12% +/- 4.58%), and idiopathic (13.74 +/- 4.20%) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12% +/- 6.25%) than extrapulmonary diffuse alveolar damage (3.93% +/- 2.86%), with this difference being statistically significant (P < 0.001). Equally significant was the difference for progressive decrease of cytokeratin AE1/AE3 immunostaining in hyaline membranes present in the extrapulmonary diffuse alveolar damage (5.42% +/- 2.80%) and idiopathic diffuse alveolar damage (0.47% +/- 0.81%) groups (P < 0.001). None of the groups stained for cytokeratin CK-7, CK-8, vimentin, or a anti-smooth muscle actin. CONCLUSIONS: This study showed that only the epithelial/endothelial components (SP-A, factor VIII, and AE1/AE3) of the alveolar/capillary barrier are present in hyaline membranes formation in the 3 groups of patients with diffuse alveolar damage. The significant difference in the expression of factor VIII-related antigen and cytokeratin AE1/AE3 in the expDA versus iDAD groups as well as the significant difference in the amount of hyaline membranes present in the pDAD versus iDAD groups are suggestive of a local and specific lesion with different pathways (direct, indirect, or idiopathic), depending on the type of diffuse alveolar damage.

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage / Imunomarcação não homogênea das membranas hialinas na sindrome da angustia respiratório do adulto pulmonar, extrapulmonar e idiopática

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (a-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65 percent ± 3.24 percent), while extrapulmonary diffuse alveolar damage (9.52 percent ± 3.64 percent) and idiopathic diffuse alveolar damage (7.34 percent ± 2.11 percent) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36 percent ± 3.12 percent), extrapulmonary (16.12 percent ± 4.58 percent), and idiopathic (13.74 ± 4.20 percent) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12 percent ± 6.25 percent) than extrapulmonary diffuse alveolar damage...

OBJETIVO: Determinar a natureza da membrana hialina nas diferentes manifestações do dano alveolar difuso [pulmonar e extrapulmonar síndrome do desconforto respiratório] e idiopático [pneumonia intersticial aguda]. MATERIAIS E MÉTODOS: Espécimes pulmonares foram obtidos de 17 pacientes com SDRA e 9 pacientes com pneumonia intersticial aguda e separados em três diferentes grupos: (a) dano alveolar difuso pulmonar (DADp) (n=8) constituído por casos de pneumonia, (b) dano alveolar difuso extrapulmonar (DADexp) (n=9) constituído por casos de sepse e choque séptico e (c) dano alveolar difuso idiopático (DADi) (n=9) constituído por casos idopáticos (ou pneumonia intersticial aguda). As características das membranas hialinas do padrão histológico de dano alveolar difuso foram examinadas usando vários tipos de anticorpos. Os anticorpos usados foram surfactante apoproteina A (SP-A), anti-citokeratina 7 (CK7), citokeratina 8 (CK8), alfa actina de músculo liso (a-SMA), citokeratina AE1/AE3 (AE1/AE3) e antígeno relacionado ao fator VIII (Fator VIII). RESULTADOS: Observaram-se aumentos maiores da quantidade de membrana hialina no dano alveolar difuso pulmonar (12.65 ± 3.24 por cento), intermediários no dano alveolar difuso extrapulmonar (9.52 ± 3.64 por cento) e baixos no dano alveolar difuso idiopático (7.34 ± 2.11 por cento) respectivamente, esta diferencia foi estatística significante entre o dano alveolar difuso pulmonar e o dano alveolar difuso idiopático (p<0.05). Não se encontrou significância estatística para a quantidade de imunomarcação de Sp-A nos grupos de dano alveolar difuso pulmonar (15.36 ± 3.12 por cento), extrapulmonar (16.12 ± 4.58 por cento) e idiopático (13.74 ± 4.20 por cento). Com relação ao Fator VIII, nós encontramos maiores aumentos da imunomarcação da membrana hialina no grupo dano alveolar difuso idiopático (14.12 ± 6.25 por cento) do que no dano alveolar difuso extrapulmonar (3.93 ± 2.86 por cento), com significância estatística (p<0.001). Da mesma...

Ultrastructural changes in arteriovenous malformations after gamma knife surgery: an electron microscopic study.

OBJECT: The authors analyzed morphological alterations at the subcellular level by undertaking transmission electron microscopy in arteriovenous malformations (AVMs) after gamma knife surgery (GKS). METHODS: Histological, immunohistochemical, and electron microscopic investigations were performed in a series of pathological specimens obtained in seven patients. The patients harbored cerebral AVMs that had been previously treated with GKS and had suffered subsequent bleeding 10 to 52 months after treatment. Histological studies revealed spindle cell proliferation in the connective tissue stroma and in the subendothelial region of the irradiated AVM vessels. Electron microscopy demonstrated different ultrastructural characteristics of this spindle cell population. There were cells with a smooth-edged oval nuclei surrounded by massive bundles of collagen fibers in the extracellular matrix. Other cells with the same nuclear morphology contained abundant intracytoplasmic filaments. Nuclear deformation was connected to a fibrillary system developed within the cytoplasm, and peripheral attachment sites were related to an extracellular layer of basement membrane-like material arranged parallel to the cell border. Also present were cells containing well-developed cisterns of rough endoplasmic reticulum and dense bodies at the periphery of the cytoplasm with folded, irregular nuclei. CONCLUSIONS: The ultrastructural and histological characteristics of the spindle cell population in the GKS-treated AVMs are similar to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Because similar cell modifications have not been demonstrated in control nonirradiated AVM specimens, these myofibroblasts may contribute to the shrinking process and final occlusion of AVMs after radiosurgery.

Removal of hyaline articular cartilage reduces lymphocyte infiltration and activation in rheumatoid synovial membrane.

OBJECTIVE: To analyze the effect of removal of hyaline articular cartilage on synovial membrane pathology in chronic arthritis. METHODS: Synovial membrane samples were obtained from patients with rheumatoid arthritis or ankylosing spondylitis in association with total hip arthroplasty, either primary or revision surgery. Synovial membrane histopathology was assessed by immunochemical staining and morphometry. RESULTS: CD68 positive macrophages were common in revision synovial membranes. In contrast, T lymphocytes were much more common in primary rheumatoid synovial membranes (p < 0.001). Many T lymphocytes in primary synovial membrane were HLA-D/DR positive (p < 0.001) and interleukin 2 receptor (IL-2R) positive (p < 0.001) and contained interferon-gamma(IFN-gamma; p < 0.001) and tumor necrosis factor-beta (TNF-beta; p < 0.001). In contrast, revision synovial membranes from patients with chronic arthritis contained only a few HLA-D/DR positive T cells and practically no IL-2R, IFN-gamma, or TNF-beta positive activated T lymphocytes. CONCLUSION: The components of hyaline articular cartilage may be the source of autoantigen responsible for perpetuation of chronic arthritides.

Human monoclonal rheumatoid synovial B lymphocyte hybridoma with a new disease-related specificity for cartilage oligomeric matrix protein.

Joint-specific self-Ags are considered to play an important role in the induction of synovial T and B cell expansion in human rheumatoid arthritis (RA). However, the nature of these autoantigens is still enigmatic. In this study a somatically mutated IgG2 lambda B cell hybridoma was established from the synovial membrane of an RA patient and analyzed for its Ag specificity. A heptameric peptide of cartilage oligomeric matrix protein (COMP) could be characterized as the target structure recognized by the human synovial B cell hybridoma. The clonotypic V(H) sequences of the COMP-specific hybridoma could also be detected in synovectomy material derived from five different RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of V(H) genes closely related to those coding for a COMP-specific Ag receptor in RA synovial B cells. Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is likely to reflect local immune responses toward a cartilage- and tendon-restricted Ag that might be crucial to the induction of tissue damage in RA.

Oncocytic hepatocellular carcinoma with numerous globular hyaline bodies.

Two well circumscribed tumors, oncocytic and non-oncocytic, were removed from the non-cirrhotic liver of a 67 year old male. The large oncocytic tumor (OCT), occupying the entire left lobe, was multilobulated with focal coagulation necrosis and areas of hemorrhage. Light microscopy revealed that it consisted of exclusively large, granular oxyphilic cells with moderate nuclear atypia and occasional mitotic figures, which were trabecular and/or pseudoglandular in structure, but no lamellar fibrosis was seen. Characteristically, the OCT cells included numerous globular hyaline bodies (GHB) of various sizes which were stained red with acid fuchsin and deep blue or magenta with phosphotungstic acid hematoxylin (PTAH), but negative for periodic acid Schiff (PAS), orcein, rhodamine and Grimelius methods. Immunohistochemically, alpha-fetoprotein (AFP), alpha-1-antitrypsin, alpha-1-antichymotrypsin, fibrinogen and ferritin were all negative. On ultrastructural examination, tumor cells were mitochondria-rich, including electron dense, ovoid or polyhedral inclusions, with the delineated membrane identical with that of the GHB. In contrast, the small tumor in the right lobe (Segment 7) was a solid adenoma with no oncocytic transition. Based on these findings, it was postulated that OCT consists of heterogenous proliferation of mitochondria-rich hepatocytes which tend to induce lysosomal GHB closely associated with mitochondrial abnormalities.

Basal cell carcinoma with hyaline inclusions.

A 69 yr old man had a 4 mm basal cell carcinoma completely excised from the chin. Numerous hyaline cytoplasmic inclusions were contained within the tumor cells. The inclusions stained intensely red with Masson's trichrome, and immunocytochemically there was prominent rim labelling for keratins (bovine, callus and AE1/3) and muscle-specific actin, the latter more faintly decorating the centre of some inclusions. The inclusions were negative for antibodies to cytokeratin Cam5.2, epithelial membrane antigen (EMA), vimentin, S100, neurofilaments, glial fibrillary acidic protein (GFAP) and carcinoembryonic antigen (CEA) and there was no post Congo red apple green birefringence to indicate amyloid. Ultrastructure indicated the inclusions were composed of proteinaceous material surrounded by a defined rim of tonofilaments in cells showing no degenerative features. The findings suggested aberrant tumor cell keratinization. Familiarization with this rare variant of a common cutaneous carcinoma will alleviate diagnostic difficulties that may arise, particularly in superficial tumor curettage.

Immunocytochemical and ultrastructural studies of hyaline inclusions in sporadic motor neuron disease.

We investigated hyaline inclusion bodies (HI) immunocytochemically and ultrastructurally in six cases of sporadic motor neuron disease (MND). All HI contained large amounts of ubiquitin and some HI were stained at the core or the center with anti-neurofilament antibody, with the surrounding halo unstained. No HI were stained with antibodies raised against cytoskeletal proteins such as high-molecular weight microtubule-associated proteins and phosphorylated tau. Ultrastructurally, HI were chiefly composed of filaments measuring about 20 nm in diameter thicker than neurofilaments, and contained fine granules and frequently one or more of four characteristic profiles, i.e., small electron-dense materials resembling Bunina bodies, bundles of tubular filaments measuring approximately 20 nm in diameter, large electron-dense cores, and focal accumulations of randomly arranged neurofilaments. Hyaline inclusions can be regarded as one of the characteristic markers for sporadic MND as well as familial amyotrophic lateral sclerosis. Hyaline inclusions have a markedly heterogeneous ultrastructure and, therefore, differences in immunoreactivity with antineurofilament antibodies are not unexpected.

Immunolocalization of hyalin in sea urchin eggs and embryos using an antihyalin-specific monoclonal antibody.

Monoclonal antibodies were raised against purified cortical secretory vesicles (CVs) from the eggs of Strongylocentrotus purpuratus. One of the monoclonal antibodies (MAb 69-10, an IgA) was shown by immunofluorescence labeling of intact and detergent-lysed CVs to be directed against a CV content antigen. Immunoblot analysis of CVs revealed that MAb 69-10 bound to a major CV polypeptide with an Mr similar to that of hyalin (i.e., 300,000). MAb 69-10 was subsequently shown to bind to purified hyalin prepared from S. purpuratus and to cross react with hyalin prepared from Lytechinus pictus. Immunogold labeling on thin sections of unfertilized S. purpuratus eggs showed that hyalin was localized to the electron-lucent portion of CVs. This result is in agreement with the labeling pattern obtained by Hylander and Summers (Dev Biol 93:368-380, 1982) using polyclonal antihyalin antibodies. In fertilized eggs and later-stage embryos, hyalin was observed to be located on the external surface of the embryo. MAb 69-10 should be useful in studies of the structure of hyalin and its function in morphogenesis.

The monoclonal antibody GRC1 produced against human cornea recognizes a common determinant of collagen.

The monoclonal antibody GRC1 was obtained by immunizing BALB/c mice with human cornea. Screening was performed by indirect immunofluorescence in cryostatic sections of several tissues: cornea, skin, placenta, hyaline cartilage, blood vessels, and nerves. GRC1 was seen to recognize fibrillar structures in all of these tissues. The pattern of reaction was interstitial and membranous. On cornea, GRC1 reacts definitely with Bowman's membrane and diffusely with the stroma, while on skin it shows strongly positive reactivity with the papillary dermis and with the basement membrane. It also reacts on hyaline cartilage at the periphery of the condrocytic lacunae. These immunohistologic results suggest that GRC1 recognized human collagen. In order to investigate further the subtype of collagen defined by GRC1, an ELISA was performed with purified collagens of several types: I, II, III, IV, and V. The monoclonal antibody GRC1 defines a common determinant in types III, IV, and V.

Sea urchin morphogenesis and cell-hyalin adhesion are perturbed by a monoclonal antibody specific for hyalin.

We have generated and characterized a monoclonal antibody (McA Tg-HYL) that recognizes sea urchin hyalin as evidenced by immunofluorescence staining of the hyaline layer (HL) and immunoblot staining of the hyalin protein band. On immunoblots of HL extracts only the hyalin protein reacted with McA Tg-HYL. Immunoprecipitates of radioactive proteins from embryos incubated with [35S]methionine yielded radioactive hyalin and 190, 140 and 105 x 10(3) Mr proteins associated with hyalin. McA Tg-HYL was generated against Tripneustes gratilla embryos but reacts with hyalin from the distantly related sea urchin species, Colobocentrotus atratus, Strongylocentrotus purpuratus, Arbacia punctulata, Lytechinus variegatus and Lytechinus pictus. Developing embryos of the above-mentioned six species were treated with McA Tg-HYL and did not gastrulate or form arms. Observations of treated embryos revealed areas of separation of the hyaline layer from the underlying embryonic cells, suggesting that McA Tg-HYL was interfering with binding of the cells to the HL. Using the centrifugation-based adhesion assay of McClay et al. (Proc. natn. Acad. Sci. U.S.A. 78, 4975-4979, 1981), Fab' fragments of McA Tg-HYL were found to inhibit cell-hyalin binding. McA Tg-HYL did not inhibit hyalin gelation in vitro or the reaggregation of dissociated blastula cells. We postulate that McA Tg-HYL recognizes an evolutionarily conserved hyalin domain involved in cell-hyalin binding and required for normal epithelial folding.

Immunological abnormalities in massive cutaneous hyalinosis.

Immunological studies in a patient with massive cutaneous hyalinosis, a disease characterized by principally dermal and subcutaneous accumulations of monoclonal kappa light chains and a gliadin-binding mannose-rich 90 kD glycoprotein, show that the ratio of helper to suppressor T cells is decreased and the proliferative responses of the peripheral mononuclear cells to T cell and T cell-dependent B cell mitogens are depressed. High levels of circulating immune complexes were demonstrated by C1q-binding and rheumatoid factor enzyme linked immunoassays. IgM and IgA class antibodies against the hyalin components, the mannosyl-90 kD glycoprotein and type I collagen, and against keratin and gluten were present in high titres. The reactivity of mononuclear cells to phytohemagglutinin normalized and the antibody levels to hyalin proteins, keratin and gluten fell during low-dose steroid therapy. However, the concanavalin A response was not reversed, neither did the levels of circulating immune complexes and anti-intercellular substance antibodies decrease. The results demonstrate a very complex dysfunction of the immune system in massive cutaneous hyalinosis.

IgM class antibodies to intercellular substance in massive cutaneous hyalinosis: occurrence and relation to antigluten and antihyalin antibodies.

High levels of circulating IgM class antibodies to intercellular substance were found in massive cutaneous hyalinosis, a systemic kappa light chain disease characterized by hyalin deposits in skin and gut. A strong humoral immune response to the accumulating mannose-rich hyalin glycoprotein and to wheat gluten was also demonstrated. Both gluten and the hyalin protein, when added to serum, abolished the immunofluorescence staining of the intercellular cement, suggesting that there may exist common antigenic sites in the hyalin protein, gluten, and intercellular substance.