Humoral immunity to cow's milk proteins and gliadin within the etiology of recurrent aphthous ulcers?

OBJECTIVES: The goal of this study was to determine the incidence of serum antibodies to gliadin and to cow's milk proteins (CMP) using ELISA test, within patients who have recurrent aphthous ulcers (RAU). SUBJECTS AND METHODS: Fifty patients with recurrent aphthous ulcers and fifty healthy people were included in this research. Levels of serum IgA and IgG antibodies to gliadin and IgA, IgG and IgE to CMP were determined using ELISA. RESULTS: The levels of serum antigliadin IgA and IgG antibodies were not significantly higher in patients with RAU in comparison with the controls (P = 0.937 and P = 0.1854 respectively). The levels of serum anti-CMP IgA, IgG and IgE antibodies were significantly higher in patients with RAU in comparison with the controls (P < 0.005, P < 0.002 and P < 0.001 respectively). In general, the increased humoral (IgA or IgG) immunoreactivity to CMP was found in 32 of 50 patients, while 17 of them showed the increased levels of both IgA and IgG immunoreactivity to CMP. At the same time, 16 out of 50 patients had IgA, IgG and IgE immunoreactivity to CMP. CONCLUSION: These results indicate the strong association between high levels of serum anti-CMP IgA, IgG and IgE antibodies and clinical manifestations of recurrent aphthous ulcers.

[Angioedema caused by angiotensin-converting enzyme inhibitors]. / Angioedem izazvan lekovima inhibitorima enzima ACE.

Angioedema is a rare, but important effect of arterial hypertension treatment with drugs which inhibit angiotensin-converting enzyme. Usually, it develops in the first week of therapy, but some atypical cases of the development of angioedema after several months to few years after the onset of the therapy have been reported. Undesired reactions caused by these drugs are probably not allergic, but they are caused by pharmacological effect of these drugs in persons with risk of allergic reaction. In this paper we present some patients with angioedema.

[T lymphocytes in allergic inflammation]. / Limfociti T u alergijskoj inflamaciji.

T lymphocytes are the crucial cells in immunopathogenesis of allergic diseases since they regulate the occurrence of allergic sensitisation, synthesis of immunoglobulin E and allergic inflammation. The importance of lymphocyte T is reflected on the fact that after activation by a specific antigen they are able to produce different cytokines responsible for activation and aggregation of specific inflammatory cells in target tissues, promoting the occurrence and maintenance of allergic inflammation. Discovery of functional dichotomy of activated lymphocytes T CD4+ capable of suppressing synthesis of immunoglobulin E (Th1) or stimulate immunoglobulin E and allergic inflammation (Th2) is an important element in elucidation of pathogenesis of allergic inflammation and inadequate synthesis of immunoglobulin E. The immunoglobulin synthesis is regulated by a complex combination of factors and signals where lymphocytes CD4+ play the central regulatory role.

[Leukotrienes in allergic inflammatory reactions]. / Leukotrijeni u reakcijama alergijske inflamacije.

Production of leukotrienes, lipooxygenase products of arachidonic acid metabolism, plays an important role in inflammatory reactions, particularly well studied in bronchial asthma. Lipooxigenase-5 and lipooxygenase-activating protein-5 are crucial in the production of leukotrienes with potent biological activities. Leukotriene B4 is a leukocytic chemoattractant and it induces aggregation and adherence of leukocytes to endothelial vasculature. Sulfidopeptid leukotrienes (C4, D4 and E4) are potent bronchoconstrictors, producing mucous secretion in the airways and increasing vascular permeability. Leukotrienes participate in the process of inflammation, as well as in early and late asthmatic responses. They are found in the blood, liquid obtained upon bronchoalveolar lavage as well as in the urine, irrespectively whether bronchospasm developed spontaneously or it was induced by an allergen. Administration of the specific leukotriene receptor antagonists or leukotriene synthesis inhibitors ameliorates the symptoms and signs of bronchial asthma.

[The role of prostaglandins in allergic inflammation]. / Uloga prostaglandina u alergijskoj inflamaciji.

Prostaglandins likewise leukotriens are proinflammatory mediators resulting from metabolic degradation of the arachidonic acid originating from membrane phospholipids. The most important products of enzyme cyclooxygenation of arachidonic acid are prostaglandins D2, E2, F2a, tromboxane A2 and prostacyclin. Prostaglandins express their tissue effects via the five basic receptor types. Within the allergic inflammation activated mast cell synthesizes prostaglandin D2 (first lipid mediator) which has bronchoconstrictive and vasodilating effects and attracts neutrophilic leukocytes. Moreover, it also participates in the late phase reactions, six hours subsequent to the exposure to the allergen. This mediator is also important in pathogenesis of urticaria, allergic rhinitis and allergic bronchial asthma. In addition to prostaglandin D2, prostaglandin F2a and tromboxane A2 also have bronchoconstrictive actions, while prostacyclin and prostaglandin E have bronchodilating effects. Inhalation of prostaglandin E prevents asthmatic attacks caused by allergens, strain, metabisulfite and ameliorates attacks of aspirin asthma, which confirms the hypothesis that aspirin asthma is based on cyclooxigenase inhibition and increased leukotriene production. In patients with atopic dermatitis, prostaglandin E has suppressive effects on Interferon gamma production by Th1 helper cells and increases production of Interleukin 4 by the Th2 cells. Tromboxane A2 plays a certain role in the development of bronchial hyperreactivity and late asthmatic response. Prostaglandins are also important mediators in the pathogenesis of allergic conjunctivitis. Most of nonsteroidal antiinflammatory drugs inhibit the enzyme cyclooxygenase and thus also prostaglandin biosynthesis and release.

[The role of thrombocytes in allergic inflammation]. / Uloga trombocita u alergijskoj inflamaciji.

The platelet has traditionally been associated with haemostasis. Participation of platelets in defence mechanisms is presentiment by the knowledge that primary haemostasis may be phylogenetic vestige retained from the behaviour of primitive leukocytes. Platelets have the ability to undergo shape change with pseudopod formation, chemotaxis, diapedesis, and phagocytose. Platelets contain a wide range highly potent inflammatory factors that are capable of inducing or augmenting certain inflammatory responses. Different surface molecules have been detected on the plasma membrane, highlight the platelets ability to bind a variety of biologic surfaces, including those of other cells, resulting in close apposition of platelets and their targets. They can interact with parasites, viruses and bacteria. Studies from several groups suggest an important role of the platelet in allergic processes. Platelets possess receptor for immunoglobulin E. Numerous clinical reports are describing the modification of biologic activity of platelets from allergic patients as compared to healthy subjects. The incidence of abnormal platelet responsiveness is in higher among patients having high serum IgE titres. Platelet depletion decreased the anaphylactic response and protects against the lethal consequences of the antigen provocation. Evidence now exists in support of primary role of the platelet in the pathogenesis of bronchial asthma. Platelets can participate in allergic asthma by acting as inflammatory cells, by releasing spasmogens and by interacting with other inflammatory cells. Thrombocytopenia and the increased plasma levels of platelet-derived markers occurred in parallel with bronchoconstriction induced by antigen provocation of allergic astmatics. Platelet depletion inhibits the ability of antigen to induce late onset airways obstruction and airway hyperresponsiveness. Platelet apheresis in human resulted in a positive clinical effect. Platelets respond to aspirin or other NSAIDs in acetyl salicylic acid sensitive asthmatics and these findings provide further evidence for role of the platelet in this form of bronchial asthma.

[The role of mononuclear phagocytes and dendritic cells in allergic inflammation]. / Uloga mononuklearnih fagocita i dendriticnih celija u alergijskoj inflamaciji.

Mononuclear-phagocytic system is a diffuse network of cells which includes monoblasts and promonocytes of the bone marrow, blood monocytes, as well as free and fixed tissue macrophage cells. In different tissues and organs macrophages acquire different morphological and functional properties under the influence of the local tissue factors. Interaction of macrophages with other cells and molecules is performed via the large number of different receptors resulting in activation of the macrophage cell, accompanied by a series of morphological and metabolic changes which potentiate all its functions. Activated macrophage cells were found in certain diseases. Macrophages and dendritic cells are associated with all aspects of immunity. Owing to their capacity to undergo phagocytosis they are of the utmost importance for unspecific defense from microorganisms. As accessory cells they also participate in cellular and humoral immunity, being at the same time effector cells owing to their capacity of antigen presentation. Moreover, they also participate in immune response regulation owing to their influence on the function of other cells, including mast cells, basophilic leukocytes and T lymphocytes, in which they may influence differentiation toward Th1 or Th2 and cytokine milieu favorable for allergic reaction. Dendritic cells are the most important antigen-presenting cells and thus, they play a major role in activation of helper T lymphocytes, and mode of antigen presentation is significant for regulation of the nature and intensity of the immune response. Pulmonary macrophage cells have been most thoroughly studied, and the observed changeability of their functional and morphological characteristics is of the utmost importance for studying of the pathogenetic properties and regulation of the chronic inflammatory response in bronchial asthma.

[Sjogren's syndrome]. / Segrenov sindrom.

Sjogren's syndrome is a chronic inflammatory disease of unknown aethiology. It is characterized by decreased secretion of salivary and lacrimal glands, which induces keratoconjunctivitis sicca and xerostomia. Sjogren's syndrome is a central autoimmune disease, and it has characteristics of both organ-specific and generalized autoimmune diseases. It can exist as a primary disease or is associated with other autoimmune diseases (most freyuently with systemic lupus erythematosus or rheumatoid arthritis) and is classified as a secondary Sjogren's syndrome. The aethiology is multifactorial, and it has not yet been completely explained. In the pathogenesis of the disease the important role have genetic predisposition, chronic oestrogen stimulation, end viral infections, especially of the herpes virus group (EBV, CMV, HHV6) and retroviruses. In the clinical picture xerostomia, xerophtalmia and non-erosive arthritis are the most common features, with the whole spectrum of extraglandular manifestations of respiratory, gastrointestinal, skin, and haematologic, neurologic and endocrinologic disturbances. Pathohistological findings of minor labial salivary gland lymphocyte infiltration is the most specific and the most sensitive diagnostic criterion of Sjogren's syndrome. The diagnosis of keratoconjunctivitis sicca is made by Schrimer's test, Rose bengal dye staining and by the "tear break up time". Differential diagnosis of Sjogren's syndrome includes an extremely large number of various pathologic states. The treatment of Sjogren's syndrome consists of symptomatic treatment of dry mucosas (artificial tears, etc.) and also of antiinflammatory drugs, glucocorticoids, immunosuppressive drugs. Plasmapheresis and intravenous administration of immunoglobulins are used for immunosuppression in these patients.

[Risk factors for allergic bronchial asthma]. / Faktori rizika za nastanak alergijske bronhijalne astme.

The paper deals with the current data on aetiological factors of allergic bronchial asthma. The cause of allergic bronchial asthma is unknown. In general, endogenous and environmental factors are though to play a certain role in its development. Early contact with allergic agents, air pollution, tobacco smoking and infective agents (viruses), are considered to be environmental factors. Endogenous factors are heredity of allergic diseases and special susceptibility for bronchial asthma.

[Behcet's disease]. / Behcetova bolest.

Behcet's disease is a recurrent, systemic inflammatory disease of the vasculitides group. It has been most frequently diagnosed in Japan and east Mediterranean countries. Its clinical picture is characterised by multiple organ and systemic defects indicating vasculitis. In addition to triple symptom of complex (recurrent ulcerations of the oral cavity and genital organs, eye lesions in the form of episcleritis, uveitis and hypopyon), other symptoms and signs are also frequent. Aetiology of the disease has not yet been completely elucidated. Immunosuprressive agents, as a single therapy or combined with glycocorticoid drugs, are used in treatment of Behcet's disease. As for the prognosis of the Behcet's disease, chronic exacerbation of the symptoms and signs is typical, and insufficiently aggressively treated posterior uveitis usually results in blindness. The prognosis is also poor in case of central nervous system and large arterial blood vessels lesions.

[Melkersson-Rosenthal syndrome]. / Melkerson-Rozentalov sindrom.

Melkersson-Rosenthal's syndrome is characterized by recurrent or persistent oedema of the lips or the face; the fissured tongue, and intermittent paralysis of the facial nerve. Oligosymptomatic forms are more common than the triad. The syndrome is rarely encountered, it is aetiologycally obscure, the laboratory findings are not specific, but differential diagnosis is very complex, especially in conditions of recurrent and hereditary angioedema. The authors report two cases of the syndrome: the first with the triad and mild neurological symptoms, and the second with two syndrome elements, oedema of the lips and the fissured tongue. Pathohistological results of the biopsy samples of oral mucosa revealed the advanced phase with granulomatous lesions in one case, and early phase with oedema of the connective tissue and perivascular lymphocyte infiltration in the second. Allergic genesis was ruled out, based on negative results of numerous laboratory and clinical tests. Glycocorticoid therapy with antihistaminics and anabolica resulted in clinical improvement.

[Angioimmunoblastic lymphadenopathy with dysproteinemia and hypothyreosis]. / Angioimunoblastna limfadenopatija s disproteinemijom i hipotireoza.

A patient with angioimmunoblastic lymphadenopathy with disproteinemia is presented. The diagnosis is made on the basis of lymph node hystology and laboratory findings of typical immunologic aberrations. The patient had signs of developed primary hypothyreosis with cardiac failure at the same time. The two diagnsis were made in the late stages of diseases, two years after the first findings of generalised lymphadenopathy and clinical signs of hypothyreosis, with developed complications in the form or cardiac, respiratory and renal failure. The disease had terminated lethaly before the pathohystologic diagnosis was known.

[Plasmapheresis in clinical practice]. / Plazmafereza u klinickoj praksi.

Plasmapheresis is an immunomodulatory procedure with immunosuppressive effect. Plasmapheresis involves taking blood, separating off the plasma and returning the red cell-enriched fraction to the patient. In plasmapheresis improvement is due to the removal of mediators of tissue damage. Therapeutic plasmapheresis has been used in many diseases in which immunological mechanisms are proved. It has been noted that there may be a "rebound" in the level of antibodies and immune complexes after plasmapheresis, perhaps due to elimination of feedback suppressor mechanisms. For that reason, plasmapheresis is only effective when used as part of an immunosuppressive regimen which also includes steroids and/or cytotoxic agents.

[Therapeutic use of human immunoglobulin]. / Terapijska primena humanih imunoglobulina.

Human immune globulin administered intramuscularly has been used for more than 40 years. In the last decade intravenous preparations were developed. They do not aggregate and contain IgG molecules with intact recognition and effector functions. These compounds are safe and only minor side effects were reported even when high doses were given. The mechanism by which intravenous gammaglobulin exacts its function is a combination of the Fc receptor blockade in the reticuloendothelial system, a marked increase in the suppressor cell function with down regulation of the antibody production and an intervention in the idiotype-antiidiotype network. Human immune globulin is an important therapeutic tool not only in the antibody deficiency, but also as an immunomodulatory agent in autoimmune disorders.