Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads to functional changes in lysosomes. Lysosomal deposition of unmetabolized glycolipid substrates stimulates the activation of pathogenic cascades, including immunological processes, and particularly the activation of inflammation. In lysosomal storage diseases, the inflammatory response is continuously being activated because the stimulus cannot be eliminated. Consequently, inflammation becomes a chronic process. Lysosomes play a role in many steps of the immune response. Leukocyte perturbation and over-expression of immune molecules have been reported in Fabry disease. Innate immunity is activated by signals originating from dendritic cells via interactions between toll-like receptors and globotriaosylceramide (Gb3) and/or globotriaosylsphingosine (lyso-Gb3). Evidence indicates that these glycolipids can activate toll-like receptors, thus triggering inflammation and fibrosis cascades. In the kidney, Gb3 deposition is associated with the increased release of transforming growth factor beta and with epithelial-to-mesenchymal cell transition, leading to the over-expression of pro-fibrotic molecules and to renal fibrosis. Interstitial fibrosis is also a typical feature of heart involvement in Fabry disease. Endomyocardial biopsies show infiltration of lymphocytes and macrophages, suggesting a role for inflammation in causing tissue damage. Inflammation is present in all tissues and may be associated with other potentially pathologic processes such as apoptosis, impaired autophagy, and increases in pro-oxidative molecules, which could all contribute synergistically to tissue damage. In Fabry disease, the activation of chronic inflammation over time leads to organ damage. Therefore, enzyme replacement therapy must be started early, before this process becomes irreversible.

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Food allergy is becoming a medical, economical and social problem. Soybean, together with milk, peanuts and eggs, are the major allergenic foods. This pathology affects the infant population, when the gut barrier is immature and the immune system is still refining its ability to tolerate food proteins. In our country, cow's milk allergy (CMA) constitutes the main food allergy in infancy, but soy allergy has become exacerbated because of the increased utilization of soy-based formulas as cow's milk (CM) substitutes and the inclusion of soy-proteins in many processed foods. Once a food allergy is diagnosed, the only proven therapy is the strict elimination of the offending allergens from the diet. Available substitutes for CM include milks from different mammalian animals, soy-based formulas, hydrolysed cow's milk proteins (CMP) and amino acid-based formulas. Furthermore, there is evidence that soy proteins may trigger allergic reactions in CMA patients, as assessed by a double-blind placebo controlled food challenge (DBPCFC) [1].Milk contains more than 50 proteins and the major ones are implicated in a number of immunologically mediated reactions [2]. Caseins and b-lactoglobulin (b-Lg) have been described as the main antigenic and allergenic components for human beings [3,4], although immunoglobulins, a-lactalbumin (a-La), and bovine serum albumin (BSA) were also found to be reactive with different isotypes of human antibodies [5,6]. Several immunoreactive epitopes have been identified in caseins [7,. Most of the epitopes present in the casein molecules are sequential since the high number of proline and hydrophobic residues (45%) in these proteins determine an undefined secondary and tertiary structure [10]. Besides, caseins tend to aggregate as a result of hydrophobic interactions to give quaternary structures [11], and this may create conformational epitopes buried in the hydrophobic interior of the micelle [7]. These epitopes are only exposed and accessible to the immune system after denaturation of the complex by digestion.A number of soy proteins that bind antibodies, especially IgE, have been identified [12,13]. The main fractions of storage globulins from seed proteins are the complexes 7S or b-conglycinin, and 11S or glycinin. The 7S complex is generally a trimer with MW 150-200 kD, whereas 11S is a hexamer with MW 300-400 kD [14]. In the 7S fraction, or b-conglycinin, several IgE-binding proteins have been identified and some of them have been purified and characterized: Gly m Bd 28K, Gly m Bd 30K, Gly m Bd 60K [15,16]. Sequence homology has been reported between these allergens and the thiol proteinase family SUMMARYSoy-based formulas are the most employed cow's milk substitutes in the treatment of cow's milk allergy in our country. Since adverse reactions have been reported in allergic patients as a consequence of exposure to soy proteins, we have investigated the possible cross-reactivity between components from soybean and cow's milk. A cow's milk specific polyclonal antiserum and casein specific m...

Immunoenzymatic methods were used to detect the presence of cross-reactive components in mammalian milks. Residual allergenic components from cow's milk could be identified in both the moderate and extensive hydrolysates analyzed. This information may be relevant to the treatment of CMA.

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Fabry disease (FD) is an X-linked disorder of glycosphingolipid catabolism that results from a deficiency of the lysosomal enzyme alpha-galactosidase A. This defect leads to the accumulation of its substrates, mainly globotriaosylceramide, in lysosomes of cells of different tissues. Different studies have shown the involvement of immunopathologies in different sphingolipidoses. The coexistence of FD and immune disorders such as systemic lupus erythematosus, rheumatoid arthritis and IgA nephropathy, has been described in the literature. The aim of this study was to evaluate the prevalence of a group of autoantibodies in a series of Argentine FD patients. Autoantibodies against extractable nuclear antigens (ENAs), double-stranded DNA, anticardiolipin and phosphatidylserine were assayed by ELISA. Lupus anticoagulants were also tested. Fifty-seven per cent of the samples showed reactivity with at least one autoantigen. Such reactivities were more frequent among males than among females. Antiphospholipid autoantibodies were detected in 45% of our patients. The high rate of thrombosis associated with FD could be related, at least in part, to the presence of antiphospholipid autoantibodies in Fabry patients. We found the presence of ENAs, which are a characteristic finding of rheumatological diseases, previous a frequent misdiagnosis of FD, in around 39% of the cases. The detection of a high level of autoantibodies must be correlated clinically to determine the existence of an underlying autoimmune disease. With the recent development of therapy, the life expectancy in FD will increase and autoimmune diseases might play an important role in the morbidity of FD.

ObjectivesThe PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation.Design and settingAnonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists’ free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed.ResultsA panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages.ConclusionsPREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.