Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease.

We compared the local intestinal immunoglobulin (Ig) secretion in six adult patients with coeliac disease and nine control subjects by perfusion of a small bowel segment under an occluding balloon and analysis of the perfusion fluid for the content of Ig and secretory component. The results were compared to the number of Ig-containing plasma cells in the test segment. There was, respectively, a two-fold and a fivefold increase in jejunal secretion rates of IgA (both monomeric and polymeric) and IgM in patients with coeliac disease compared with control subjects. The high IgA and IgM secretion rates parallel the increase of Ig-containing plasma cells in the lamina propria. In contrast, the IgG plasma cell density increase was barely significant in patients with coeliac disease and did not result in a high IgG secretion rate. The jejunal secretion rate of secretory component was significantly increased in patients with coeliac disease and no free dimeric IgA was present in the jejunal fluid. Antigliadin-IgA was detected in the serum and jejunal fluid of the six patients with coeliac disease. Antigliadin-IgA, however, was almost entirely polymeric IgA linked to secretory component in jejunal fluid, whereas 61% was dimeric IgA not linked to secretory component in serum. This result, combined with a raised secretory component secretion rate with no evidence of secretory component saturation, suggests that serum and intestinal antigliadin IgA might be of different origins in coeliac disease.     

Immunoglobulin A antibody against hepatitis B core antigen of polymeric and monomeric forms, as well as of IgA1 and IgA2 subclasses, in acute and chronic infection with hepatitis B virus

Solid-phase radioimmunoassays using monoclonal antibodies were used to assay antibody to hepatitis B core antigen of immunoglobulin A class in terms of polymeric and monomeric forms, as well as of IgA1 and IgA2 subclasses, in the serum of persons infected with hepatitis B virus. The level of secretory immunoglobulin A antibody was significantly higher in patients with acute hepatitis (mean +/- S.E., sample per normal ratio = 29.2 +/- 1.9) than that in asymptomatic carriers (2.1 +/- 0.1), patients with chronic persistent hepatitis (3.5 +/- 0.5), patients with chronic active hepatitis (6.9 +/- 1.3) or patients with cirrhosis (5.8 +/- 1.1). In acute type B hepatitis, only polymeric immunoglobulin A antibody of either IgA1 or IgA2 subclass was detected. In contrast, in chronic infection, antibody to hepatitis B core antigen of IgA2 subclass was found in the polymeric form, but antibody of IgA1 subclass was detected in both polymeric and monomeric forms.     

IgA triggers tumor necrosis factor alpha secretion by monocytes: a study in normal subjects and patients with alcoholic cirrhosis

Under endotoxin-free conditions, peripheral blood mononuclear cells and purified monocytes isolated from healthy control subjects and patients with alcoholic cirrhosis disclose elevated tumor necrosis factor alpha messenger RNA level and produce tumor necrosis factor alpha in response to stimulation by either soluble polymeric IgA or monomeric IgA bound to the surface of culture dishes but not by soluble monomeric IgA. Polymeric IgA induces tumor necrosis factor alpha secretion in a dose-dependent fashion. These results suggest that cross-linking of Fc alpha receptors on human monocytes induces the messenger RNA accumulation and the secretion of the cytotoxic and immunoregulatory cytokine tumor necrosis factor alpha. Furthermore, it is shown that lipopolysaccharide-induced tumor necrosis factor alpha secretion by peripheral blood mononuclear cells is synergistically enhanced in the presence of solid phase monomeric IgA but not in the presence of either soluble monomeric or polymeric IgA. Although increased lipopolysaccharide-induced tumor necrosis factor alpha secretion is observed at baseline in alcoholic cirrhotic patients, this synergism is also expressed in this group of patients. These observations could be of pathophysiological relevance in alcoholic cirrhosis because monomeric IgA deposits along the liver sinusoids and increased serum levels of polymeric IgA are common even in the early stages of this disease.     

Hyaluronic acid and type III procollagen peptide in jejunal perfusion fluid as markers of connective tissue turnover

Hyaluronic acid (hyaluronate, HA) and type III procollagen N-terminal peptide were measured in jejunal perfusion fluid in an attempt to elucidate the turnover of connective tissue components in the small bowel in health and disease. In healthy controls (n = 16) the average concentration of hyaluronic acid in jejunal perfusion fluid was 12.2 +/- 2 micrograms/L (mean +/- SEM); the mean serum concentration was 22 +/- 7 micrograms/L. The type III procollagen N-terminal peptide concentration in jejunal fluid was 0.12 +/- 0.02 micrograms/L; the mean serum concentration was 12 +/- 0.7 micrograms/L. The albumin concentration in perfusion fluid was, on average, 0.04% of the serum values. Patients with celiac disease (n = 7) and Crohn's disease (n = 10) had normal serum levels of HA and type III procollagen N-terminal peptide. The jejunal secretion rate of HA was significantly increased in both disease groups and on average about three times higher than that in controls. The secretion rate of type III procollagen N-terminal peptide was not altered in celiac disease but increased more than three times in Crohn's disease. Habitual alcoholics investigated after alcohol withdrawal also had significantly increased jejunal secretion of HA but not of type III procollagen N-terminal peptide. In contrast, patients with alcoholic liver cirrhosis and similar ethanol intake had normal secretion of both substances. The findings of the study indicate that the secretion of HA into the jejunal lumen in health is considerable, possibly reflecting the rapid turnover of the intestinal mucosa. The enhanced jejunal secretion of HA in patients with celiac disease and Crohn's disease may be indicative of enhanced connective tissue response due to inflammation, but signs compatible with enhanced jejunal synthesis of type III collagen are only found in Crohn's disease. The HA secretion data in alcoholics might reflect (a) the active regeneration of the intestinal mucosa when ethanol is discontinued and (b) a possible role of the liver in this activity.     

Jejunal secretion of immunoglobulins and secretory component in three patients with primitive humoral immunoglobulin deficiency

Jejunal secretion of albumin, immunoglobulins and secretory component was studied using the segmental perfusion technique with an occluding balloon, in two patients with common variable hypogammaglobulinemia and one patient with selective immunoglobulin A deficiency. Results were compared with those of twenty-two controls previously studied under the same conditions. In all three cases, jejunal secretion rate of immunoglobulin A was nil and secretion rates of albumin and immunoglobulin G were increased as compared to controls. Jejunal secretion rate of immunoglobulin M was increased in the patient with selective immunoglobulin A deficiency, normal in one case of common variable hypogammaglobulinemia and almost nil in the other case. Secretory component was secreted in the jejunal lumen mostly or exclusively under a free form depending on partial or total absence of immunoglobulin A and M. This study allowed to confirm in vivo that secretion of secretory component is independent of the presence of immunoglobulins. Intestinal perfusion might be a useful tool in the investigation of immunological diseases of the intestinal tract.     

Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics.

Patients with alcoholic liver cirrhosis (ALC) have high serum levels and spontaneous in vitro production of immunoglobulin (Ig) A. Deposits of IgA are also found in liver sinusoids. Increased interleukin 6 (IL-6) production is another feature of this disease. This study shows a linear correlation between increased lipopolysaccharide (LPS)-induced IL-6 production and increased spontaneous IgA and IgG secretion by peripheral blood mononuclear cells (PBMCs). PBMCs and purified monocytes isolated from healthy control subjects and patients with ALC contain elevated IL-6 messenger RNA levels and produce IL-6 in response to stimulation with soluble polymeric IgA (p-IgA) or attached monomeric IgA (m-IgA) but not with soluble m-IgA. The addition of monospecific antibody to human IL-6 inhibits spontaneous IgA production by PBMC. This inhibition is more pronounced in patients with ALC. These data provide evidence that IgA, possibly by attachment to cells possessing Fc alpha receptors and secreting IL-6, is involved in the production of this major mediator and the amplification of Ig secretion. Circulating IgA and IgA deposits could therefore initiate a process of autoamplification implicated in the development of hypergammaglobulinemia in ALC.     

Properties of immunoglobulin A in serum of individuals with liver diseases and in hepatic bile

In comparison with normal individuals, sera of patients with alcoholic cirrhosis and other liver diseases had two to four times higher levels of immunoglobulin A and three to ten time higher levels of polymeric immunoglobulin A. The possible participation of the liver in the selective removal of polymeric immunoglobulin A from serum into bile was investigated by analyzing immunoglobulin A in serum and bile specimens obtained from a group of patients with T-tube drainage of the common bile duct. Gel filtration revealed three principal fractions of biliary immunoglobulin A: secretory immunoglobulin A with J chain and secretory component; polymeric immunoglobulin A associated with J chain; and monomeric immunoglobulin A devoid of J chain and secretory component. Secretory component-complexed immunoglobulin A composed only 50% or less of the total biliary immunoglobulin A. In comparison with immunoglobulin G, polymeric forms of immunoglobulin A appeared to be selectively transported into bile whereas monomeric immunoglobulin A was not. These data suggested that the liver selectively transports polymeric immunoglobulin A from serum into bile by both secretory component-dependent and -independent mechanisms.     

Increased spontaneous and lymphokine-conditioned IgA and IgG synthesis by B cells from alcoholic cirrhotic patients.

Immunoglobulin secretion by B lymphocytes is a complex process in which lymphokines secreted by T lymphocytes play an important regulatory role. Increased serum levels of IgA and IgG have been characteristically detected in patients with alcoholic cirrhosis. We have studied the functional alterations of T and B lymphocytes implicated in the physiopathology of this common immunoglobulin abnormality. After activation with phytohemagglutinin, purified T cells from alcoholic cirrhotic patients showed significantly enhanced secretion of B-cell differentiation factors for IgG and IgA with respect to those secreted by T cells from healthy controls (p less than 0.05). Simultaneously, normal secretion of B-cell differentiation factor for IgM was demonstrated in T lymphocytes from these patients. The pattern of secretion of the lymphokines involved in the regulation of the B-cell differentiation pathway found in alcoholic cirrhotic patients was different from that of the primary biliary cirrhotic patients studied. Purified B cells from patients with alcoholic cirrhosis secreted significantly higher amounts of IgA and IgG than did those found in healthy controls, both spontaneously (p less than 0.05) and after sequential activation with immunoglobulin ligands (Staphylococcus aureus Cowan I) and a standard B-cell differentiation factor preparation (p less than 0.05). By contrast, the IgM secretion and regulatory pathway were normal in alcoholic cirrhotic patients. These results support a physiopathological explanation for the characteristic hyperimmunoglobulinemia found in patients with alcoholic cirrhosis.     

Effect of intrajejunal elemental diet perfusion on jejunal secretion of immunoglobulins, albumin, and hyaluronan in man.

The aim of this work was to study the jejunal secretion of immunoglobulins (Ig), albumin, and hyaluronan in response to jejunal perfusion of an elemental diet. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with a control electrolyte solution for 80 minutes and with an elemental diet (containing 20.5 milligrams of free amino acids and 104.2 milligrams of oligosaccharides) for 100 minutes. The jejunal fluid concentrations of albumin, IgG, monomeric IgA (m-IgA), polymeric IgA (p-IgA), IgM, secretory component, and hyaluronan were measured and their jejunal outputs calculated. Within 20 minutes of starting perfusion with the elemental diet there was a significant increase in the secretion rates of albumin (x3.3), IgG (x5), M-IgA (x3.7), p-IgA (x2), IgM (x2), and secretory component (x1.6), but the hyaluronan secretion rate was not changed. The increase in m-IgA, p-IgA, IgM, and secretory component output suggests that intestinal perfusion of an elemental diet results in stimulation of secretory immunity. The increase in albumin and IgG output probably reflects a nutrient induced leakage from the plasma compartment.     

血清免疫球蛋白诊断乙型肝炎相关肝硬化的价值

目的评价血清免疫球蛋白G（1gG）、免疫球蛋白A（IgA）、免疫球蛋白M（IgM）诊断肝硬化的价值。方法慢性乙型肝炎172例，其中病理诊断为肝硬化的患者28例，非肝硬化患者144例。统计分析采用SPSS12．0软件；血清IgG、IgA和IgM水平诊断肝硬化的评价采片jROC曲线法。结果血清IgG、IgA和IgM水平诊断肝硬化的ROC曲线下面积分别为0．764（95％CI=0．670～0．857）、0．670（95％CI=0．566～0．773）和0．557（95％CI=0．449～0．664）。血清IgG和IgA水平诊断肝硬化的最佳截断值分别为16．85g／L和1．89g／L，其诊断肝硬化的灵敏度、特异度、阳性预测值、阴性预测值、准确度、Youden指数分别为0．821和1．000、0．660和0．285、0．319和0．214、0．950和1．000、0．686和0．401、0．481和0．285。结论血清IgG水平可作为否定诊断肝硬化的参考指标；虽然血清IgA水平也有一定否定诊断肝硬化的价值，但其可靠性很差；血清IgM水平没有诊断肝硬化的意义。     

Total serum bile acids, gamma-glutamyl transferase, prealbumin, and tyrosine: sensitive serum markers of hepatic dysfunction in alcoholic liver cirrhosis

Of 33 components analyzed in overnight fasting serum from 30 patients with alcoholic liver cirrhosis, portal hypertension, and bleeding esophageal varices, total serum bile acids, gamma-glutamyltransferase, prealbumin, and tyrosine were the most frequently abnormal 'liver tests'. Total serum bile acids correlated significantly with bilirubin, immunoglobulin M, threonine, glycine, methionine, and tyrosine. Gamma-glutamyltransferase correlated with aspartate aminotransferase, glutamine, and alanine. Prealbumin correlated with albumin and immunoglobulins G and A. Tyrosine correlated with total bile acids, orosomucoid, and 10 amino acids. The amino acid ratio of valine + isoleucine + leucine to tyrosine + phenylalanine was lowered in all patients. It is concluded that the clinical picture and pattern of serum components in patients with alcoholic liver disease are influenced by many complex pathophysiological mechanisms.     

Massive plasma cell infiltration of the digestive tract. Secretory component as the rate-limiting factor of immunoglobulin secretion in external fluids

A 29-yr-old Tunisian man had a clinical immunoproliferative small intestinal disease, different from alpha-chain disease. Serum contained 52.5 mg/ml of polymeric immunoglobulin A (IgA). Immunohistochemistry revealed a massive diffuse polyclonal IgA (99%)-plasma cell infiltration in the small bowel mucosa, with a smaller increase of IgA-producing cells in gastric and colonic mucosae. Secretory IgA levels were normal in jejunal and bronchoalveolar secretions. However, both fluids contained polymeric IgA devoid of secretory component, and free secretory component was absent. This suggests that secretory component was the limiting factor in transport of IgA in the secretions. A relative deficiency in secretory component, as compared with the huge supply of polymeric IgA, may have limited the secretory component-mediated active transport of IgA into secretions. This resulted in the appearance of high levels of polymeric IgA, unlinked to secretory component, both in serum and in the jejunal and bronchoalveolar fluids.     

Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis

Anti-mitochondrial antibodies (AMAs) have long been recognized as a serological hallmark of primary biliary cirrhosis (PBC). Although high titers of immunoglobulin (Ig)A AMAs are found in bile, saliva, and urine of patients, a pathogenic role for this antibody has remained elusive. Functional studies of this IgA in general have been impeded by low quantities of antibody and the inability to recover antigen-specific IgA in dimeric form. Using a newly defined synthetic group A. Streptococcus derived peptide, we purified large quantities of dimeric and monomeric IgA from patient sera. The purified IgA was incubated with Madine-Darby canine kidney (MDCK) cells transfected with the human polymeric Ig receptor (pIgR) and the cells studied by flow cytometric analysis for binding of carboxyfluorescein conjugated VAD-fmk peptide to activated caspase enzymes. A total of 87% of PBC patients that were anti-PDC-E2 positive had serum IgA that increased caspase activation in MDCK-pIgR+ cells compared to serum-derived IgA from controls with a maximum reaction 48 hours after addition of IgA. The titer of anti-PDC-E2 IgA among the PBC patients strongly correlated with caspase activation (cc = 0.88). Pre-absorption of the IgA using recombinant 2-oxo-acid dehydrogenase complex significantly diminished this activation. IgG from the same PBC patients did not induce caspase activation. These data suggest that during transcytosis through pIgR-positive cells, exposure to PDC-E2-specific dimeric IgA results in the initiation of caspase activation. In conclusion, we propose that due to an even greater concentration of dimeric IgA in biliary and mucosal secretions, constant transcytosis would render the exposed cells more susceptible to apoptosis resulting in subsequent bile duct damage.     

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.     

Urinary orosomucoid excretion rate in patients with non-insulin-dependent diabetes mellitus

Urinary excretion rate and clearance of alpha 1-acid glycoprotein (orosomucoid), a major serum glycoprotein which is more anionic (pI 2.7) than albumin (pI 4.7) were measured by RIA in timed overnight urine samples from non-insulin-dependent diabetic patients with different urinary albumin excretion rate and from healthy controls. The 50th percentiles of urinary orosomucoid excretion rate in patients with normo-, micro-, and macroalbuminuria were larger than those in healthy controls. Urinary excretion rate and clearance of orosomucoid increased in parallel with increase in albumin excretion rate in diabetic patients with an albumin excretion rate of more than 10 micrograms/min. On the basis of their levels of urinary orosomucoid excretion, patients with normoalbuminuria of less than 10 micrograms/min could be divided into two groups, one with a normal and the other with an elevated urinary orosomucoid excretion rate. The findings suggest that kidneys of diabetic patients with an albumin excretion rate of more than 10 micrograms/min are unable to distinguish the difference in pI between albumin and orosomucoid, and that a subgroup with an elevated orosomucoid excretion rate may be present among diabetics with normoalbuminuria.     

Molecular forms of IgA produced by various lymphoid tissues--analysis using high speed liquid chromatography

Molecular forms of immunoglobulin A (IgA) produced by cultured cells from various human lymphoid tissues were analyzed using high speed liquid chromatography (HLC). IgA secreted into culture media was easily separated into polymeric and monomeric forms by HLC. HLC has the advantages of high resolution, reproducibility, rapidity and technical simplicity in the separation of polymeric and monomeric IgA. Peripheral blood lymphocytes and cells from gut-associated lymphoid tissues, such as mesenteric lymph nodes or large bowel mucosa, secreted predominantly polymeric IgA, whereas lymphoid cells from bone marrow produced mainly monomeric IgA. Spleen cells and tonsillar cells produced nearly equal proportions of polymeric and monomeric IgA. These results suggest that with regard to IgA in serum, the polymer may originate from the gut-associated lymphoid tissues and the monomer may mostly derive from the bone marrow.     

Increased urinary orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes

ObjectivesIncreased urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients with type 2 diabetes and normal or increased UOER.MethodsWe performed a cross-sectional study of 40 patients with type 2 diabetes (normal UOER, n=16; increased UOER, n=24) who displayed no signs of cardiovascular disease and 21 healthy control persons. The renal clearance values of [⁵¹Cr]ethylenediaminetetraacetic acid ([⁵¹Cr]EDTA), lithium, orosomucoid, albumin, and sodium were measured.ResultsPatients with type 2 diabetes had normal glomerular filtration rate (GFR) measured by [⁵¹Cr]EDTA clearance. The clearance value of orosomucoid was highly increased in patients with increased UOER. The clearance values of albumin were similar in patients with increased UOER and in healthy controls. Investigations of renal tubular function revealed normal and similar levels of lithium clearance and proximal and distal reabsorption of sodium and water. Serum values of orosomucoid were higher in patients with increased UOER than in healthy controls (P<.001), but were still within reference limits, suggesting chronic low-grade inflammation. UOER was associated with increasing values of orosomucoid clearance (P<.0001) independently of serum orosomucoid.ConclusionsPatients with type 2 diabetes and increased UOER had normal GFR and showed no signs of renal glomerular or tubular dysfunction. We therefore hypothesize that increased levels of UOER may be caused by local renal production of orosomucoid due to chronic low-grade inflammation.     

Demonstration of intrapleural immunoglobulin synthesis by agarose gel isoelectric focusing. A new specific method for the diagnosis of pleural effusions of inflammatory origin?

In order to demonstrate an intrapleural immunoglobulin (Ig) synthesis, pleural effusions and serum from 14 patients with pleural effusions of various causes (inflammatory condition, malignancies, primary lung cancers, pleural metastasis, and congestive heart failure) were investigated by agarose gel isoelectric focusing (AIEF), antiserum immunofixation with monospecific antiserum against IgG and IgA, and quantitative estimation of IgG and IgA. Intrapleural immunoglobulin synthesis was assumed to occur in patients with oligoclonal Ig limited to the pleural compartment or in patients with a raised IgG index, equal to (pleura/serum IgG):(pleura/serum albumin), or a raised IgA index, equal to (pleura/serum IgA):(pleura/serum albumin). Two of 3 patients with rheumatoid pleuritis had a polyclonal intrapleural immunoglobulin synthesis demonstrated by the presence of a raised IgG and IgA index without any signs of oligoclonal Ig production on AIEF. Two of 3 patients with assumed tuberculous pleuritis had, despite a normal IgG and IgA index, an oligoclonal intrapleural IgG production detected by AIEF. This oligoclonal reaction was shown by absorption studies with Mycobacterium tuberculosis antigen to be directed against M. tuberculosis. No signs of intrapleural immunoglobulin synthesis were found in the other 10 patients investigated.     

Lack of simian immunodeficiency virus (SIV) specific IgA response in the intestine of SIV infected rhesus macaques

BACKGROUND: Little is known about secretory immunity-the major defence mechanism at mucosal surfaces-in human immunodeficiency virus (HIV) infected patients, especially in the early stages of the disease. AIMS: The aim of the study was to analyse mucosal immunoglobulin production and simian immunodeficiency virus (SIV) specific antibody response in the intestinal mucosa during the course of SIV infection in comparison with serum and saliva. ANIMALS AND METHODS: IgG, IgA, and IgM concentrations were determined in supernatants of short term cultured duodenal biopsies, serum, and saliva from SIV infected rhesus macaques (n=8) and controls (n=2) by ELISA at defined times before and after infection. Specific antibodies to SIV were detected by western blot and/or dot blot analysis. In addition, rectal swabs from two uninfected and 12 SIV infected rhesus macaques (seven without and five with enteritis) were analysed for albumin and IgG concentrations. RESULTS: An increase in total intestinal IgG and a decrease in IgA were observed. SIV specific IgG or IgA responses were detectable as early as one week after SIV infection in the serum of seven of eight animals. In contrast, intestinal SIV specific IgG production was detected only four weeks after infection in six of eight animals, and intestinal SIV specific IgA was not produced in the intestine at any time point. In saliva, the secretory component on SIV specific IgA was only detected in one animal at week 24 after infection. Enteritis is frequent in SIV infected animals and results in a significant increase in albumin and IgG secretion into the intestinal lumen. CONCLUSION: Despite modest quantitative changes in mucosal immunglobulin production there was a total lack of SIV specific IgA synthesis in the intestine during SIV infection. This lack or disturbed secretory SIV specific IgA response at mucosal surfaces may explain the rapid and high HIV/SIV replication in this compartment. In addition, our investigations indicate secretion of serum proteins into intestinal fluids during SIV infection. Previous investigations using intestinal secretions or swabs for analysing quantitative and specific immunglobulins therefore should be interpreted with caution.     

A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis.

BACKGROUND & AIMS: The aim of this study was to determine if colchicine or methotrexate improves blood test results, symptoms, and/or liver histology in patients with primary biliary cirrhosis. METHODS: Patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase (ALP) levels were at least 2 times above normal and who were not yet candidates for liver transplantation received colchicine or methotrexate and were followed up for 2 years. RESULTS: In patients receiving colchicine (n = 43), mean pruritus score decreased from 1.63 to 1.12 (P = 0.04), ALP level from 494 to 355 U/L (P < 0.0001), and alanine aminotransferase (ALT) level from 79 to 61 U/L (P < 0.0001). In patients receiving methotrexate (n = 42), pruritus score decreased from 1.25 to 0.44 (P = 0.0001), ALP from 478 to 235 U/L (P < 0.0001), and ALT from 96 to 61 U/L (P = 0.0001). Methotrexate but not colchicine significantly improved liver histology (P = 0.005) and serum immunoglobulin G levels (P = 0.0002). Methotrexate improved most blood test results more than colchicine. Serum bilirubin levels increased slightly with each drug, and albumin levels decreased slightly. CONCLUSIONS: Both colchicine and methotrexate improved biochemical test results and symptoms in primary biliary cirrhosis, but the response to methotrexate was greater.