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Biomedical subjects

M Hvatum

Publications and source records attributed to M Hvatum.

13 recordsLinked to original sources

The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis.

BACKGROUND AND AIMS: Patients with rheumatoid arthritis (RA) often feel there is an association between food intake and rheumatoid disease severity. To investigate a putative immunological link between gut immunity and RA, food antibodies were measured in serum and perfusion fluid from the jejunum of RA patients and healthy controls to determine the systemic and mucosal immune response. METHODS: IgG, IgA, and IgM antibodies to dietary antigens were measured in serum and jejunal perfusion fluid from 14 RA patients and 20 healthy subjects. The antigens originated from cow's milk (alpha-lactalbumin, beta-lactoglobulin, casein), cereals, hen's egg (ovalbumin), cod fish, and pork meat. RESULTS: In intestinal fluid of many RA patients, all three immunoglobulin classes showed increased food specific activities. Except for IgM activity against beta-lactoglobulin, all other IgM activities were significantly increased irrespective of the total IgM level. The RA associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently raised, with no significant increase against gliadin and casein. Considerable cross reactivity of IgM and IgA antibodies was documented by absorption tests. Although intestinal IgG activity to food was quite low, it was nevertheless significantly increased against many antigens in RA patients. Three of the five RA patients treated with sulfasalazine for 16 weeks had initially raised levels of intestinal food antibodies; these became normalised after treatment, but clinical improvement was better reflected in a reduced erythrocyte sedimentation rate. CONCLUSIONS: The production of cross reactive antibodies is strikingly increased in the gut of many RA patients. Their food related problems might reflect an adverse additive effect of multiple modest hypersensitivity reactions mediated, for instance, by immune complexes promoting autoimmune reactions in the joints.

Adult↗

Kinetic retrieval of eosinophil cationic protein, hyaluronan, secretory IgA, albumin, and urea during BAL in healthy subjects.

Determination of absolute concentrations of various soluble components of the epithelial lining fluid (ELF) may be valuable to estimate inflammatory activities within the underlying lung tissue. Internal standards may then be used as markers of dilution of bronchoalveolar lavage (BAL). The aim of this study was to determine whether different dwell times would affect the relationship between the concentrations of any of the three potential internal standards (secretory IgA [SIgA], albumin, and urea), and the concentrations of two potential markers of inflammation (eosinophil cationic protein [ECP] and hyaluronan [HA]) in BAL. A series of aliquots of BAL fluid were aspirated every 60 s up to 8 min after a bolus instillation of saline solution in 20 healthy subjects (10 smokers). The BAL concentrations of albumin and urea increased with time, consistent with continuous diffusion from the body water pool, absorption of the BAL fluid, or both. The rate constant of diffusion was 1,000 times higher for urea than for albumin (3.38 x 10(-1) and 3.64 x 10(-4), respectively), reflecting the difference in molecular weights, and in agreement with the notion that albumin and urea appeared in BAL fluid by a rate-limited procedure related to osmotic transfer. Biexponential increases of SIgA were recorded, suggesting a two-compartmental origin of this compound, normally located to mucosal membranes and presumed to be dissolved in ELF. Time-dependent increases in BAL fluid of HA also were recorded, but on the other hand, the ECP concentrations tended to level off after an initial increase, suggesting that the bulk of ECP appeared in BAL by a nonosmotic mechanism. We conclude that the kinetics of these three internal standards in BAL fluid differs greatly from each other and from the kinetics of the two selected markers of inflammation. Consequently, internal standards for determination of absolute concentrations of markers of inflammation in ELF should be carefully selected because of the requirement of matched kinetics of the markers.

Adult↗

Increased jejunal secretory IgA and IgM in ankylosing spondylitis: normalization after treatment with sulfasalazine.

OBJECTIVE: To investigate the intestinal immune system in patients with ankylosing spondylitis (AS) and the influence of sulfasalazine treatment. METHODS: Total IgA, secretory IgA and IgM and secretory component were determined in jejunal perfusion fluid in 19 patients with AS before and after 3 months' treatment with sulfasalazine and compared with 18 healthy control subjects. Serum immunoglobulins and inflammatory activity were measured with standard methods and compared with a clinical scoring of disease activity. RESULTS: Total IgA, secretory IgA, IgM and secretory component were significantly increased in the lavage fluid when compared with healthy controls. Treatment with sulfasalazine normalized these alterations. CONCLUSION: Our findings demonstrate that the intestinal immune system is activated in AS and that such activation can be influenced by treatment. This observation supports the idea that antigenic stimulation in the gut is a possible causative event in AS.

Adult↗

Pitfalls in determining IgG and IgG subclass antibodies to food antigens.

Several variables were found to influence enzyme-linked immunosorbent assay (ELISA) measurements of IgG and IgG subclass antibodies to food antigens. Two polyclonal rabbit antibody reagents to human IgG, and two sets of murine monoclonal antibodies to human IgG subclasses, were compared as secondary reagents. The choice of both polyclonal and monoclonal reagents affected significantly the results. High levels of IgA to an antigen depressed the measurements of comparable total IgG antibodies but did not influence the percentages of the four IgG subclass activities. Different ways of expressing the IgG subclass results were compared and the validity of the reference measurements used to obtain them was examined. Information from previous studies, together with the present data, suggests that absolute values cannot be reliably determined. We have therefore chosen to express the results for IgG subclass activities on a relative basis with reference to units of total IgG activity against the same antigen in each subject. This approach is practical and appears scientifically acceptable but limits the use of such determinations to comparisons between groups of subjects studied in the same laboratory.

Adolescent↗

Association of subepithelial deposition of activated complement and immunoglobulin G and M response to gluten in celiac disease.

Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (IgG) and M (IgM) antibodies to gluten. Intake of dietary gluten may hence induce local complement activation and mucosal damage. Jejunal tissue sections from adult patients with celiac disease were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and the terminal complement complex (TCC). Subepithelial deposition of TCC was observed in 93% of 28 untreated and in 57% of 23 partly treated study subjects. The immunofluorescence staining intensity was well correlated with the serum level of gluten-specific IgG and IgM (but not IgA), the number of mucosal IgG-producing cells, and the degree of villous atrophy. Similar immune deposits were not observed in 5 successfully treated patients with celiac disease, 5 patients with dermatitis herpetiformis without jejunal villous atrophy, and 90% of 21 control patients with histologically normal jejunal mucosa. Gluten challenge increased the amount of subepithelial TCC and produced additional C3b deposition, suggesting recent complement activation. Ingested gluten might thus, via Ig-mediated subepithelial complement activation, damage the surface epithelium in celiac disease and induce compensatory crypt hyperplasia.

Adolescent↗

Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease.

Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha-lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy.

Adolescent↗

Both IgA subclasses are reduced in parotid saliva from patients with AIDS.

Secretory IgA (SIgA), the isotypes IgA1 and IgA2, and IgM were measured by ELISA in stimulated parotid saliva from patients with AIDS (n = 16), subjects with asymptomatic HIV infection (n = 28), and HIV-seronegative healthy controls (n = 19). SIgA was significantly reduced in the AIDS group (10.4 micrograms/ml) compared with the asymptomatic HIV-infected subjects (17.1 micrograms/ml) and the controls (23.0 micrograms/ml). This decrease comprised both IgA1 and IgA2 to a similar extent on a relative basis. The SIgA decrease in AIDS patients was in striking contrast to their serum IgA level, which was significantly increased (6.9 g/l) compared with the asymptomatic HIV-infected subjects (2.9 g/l) as well as the controls (2.8 g/l). Low parotid output of SIgA in patients with HIV infection was associated with low numbers of CD4+ lymphocytes in peripheral blood as well as the presence of oral infections. The parotid output of IgM was similar in all groups. A low level of SIgA in the external secretions of patients with AIDS may well contribute to their frequent mucosal infections of opportunistic microorganisms.

Acquired Immunodeficiency Syndrome↗

Antibodies against dietary antigens in rheumatoid arthritis patients treated with fasting and a one-year vegetarian diet.

OBJECTIVE: To compare serum antibody activity against dietary antigens in patients with rheumatoid arthritis (RA) and healthy controls, and to examine whether anti-food antibody activity fluctuated with disease activity during a trial of fasting followed by a one-year vegetarian diet. METHODS: Serum IgG, IgA and IgM antibody activity against several food antigens was measured by an enzyme immunoassay. Abnormally high antibody activity was defined as values above the 90th percentile of the measurements in 30 healthy controls. Serum IgE antibody activity was measured by a radioallergosorbent test. RESULTS: During the trial 10 of 27 patients suspected that certain food items aggravated their arthritis symptoms. Elevated antibody activity against one or more of the dietary antigens was found in all RA patients, but these measurements could not be used to predict which food would aggravate the symptoms. Elevated IgG and IgA antibody activity against alpha-lactalbumin was found in a significantly larger number of RA patients than in controls. With the exception of one patient, there was no concordance between the clinical course and antibody activity against the various dietary antigens. CONCLUSION: The results indicate that a systemic humoral immune response against food items is probably not involved in the pathogenesis of RA.

Adult↗