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Background/Aim: We recently reported that renal tubular acidosis (RTA) in Sjögren’s syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. Methods: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. Results: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. Conclusion: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.

In our previous studies, we demonstrated that during Trichinella spiralis infection, T helper (Th) 2 cells contribute to the development of intestinal muscle hypercontractility and worm expulsion from the gut via STAT6. In addition, we have linked the altered muscle contractility to the eviction of the parasite and thereby to the host defense. However, the initial events linking infection to the development of muscle hypercontractility are poorly understood. In this study, we examined the contribution of CD40-CD40 ligand (CD40L) interaction in the development of intestinal muscle hypercontractility, in monocyte chemoattractant protein-1 (MCP-1) production, and in the Th2 response in CD40 ligand-deficient (CD40L -/-) mice infected with T. spiralis. Expulsion of intestinal worms was substantially delayed in CD40L -/- mice compared with the wild-type mice after T. spiralis infection. Consistent with delayed worm expulsion, there was a significant attenuation of intestinal muscle contractility in CD40L -/- mice. Infected CD40L -/- mice also exhibited marked impairment in the production of MCP-1, IL-4, IL-13, IgG1, IgE, and mouse mucosal MCP 1 (MMCP-1), and in goblet cell response. These results demonstrate that CD40-CD40 ligand interaction plays an important role in MCP-1 production, Th2 response, intestinal muscle hypercontractility, and worm expulsion in nematode infection. The present data suggest that the early events leading to the generation of Th2 response include CD40-CD40 ligand interaction, which subsequently influences the production of Th2 cytokines, most likely via upregulation of MCP-1.

A study was conducted to determine whether intraperitoneal and oral administration of formalin-fixed gram-negative bacteria induced immunohistologicallyand ultrastructurally evident glomerular deposition of IgA and C3 in C3H/HeNmice. Separate treatments with strains of Pseudomonas aeruginosa, Escherichiacoli, Haemophilus influenzae, Klebsiella pneumoniae, and two kinds of lipopolysaccharide (LPS) were used. Two mice in each treatment group were sacrificed at10,20 and 30 weeks of age to examine sequential glomerular changes. In additionto the intraperitoneal administration (IP) groups receiving whole formalin-fixedbacterial cells, cell precipitate and supernatant fractions of each bacterial strainafter sonication were injected intraperitoneally once a week, and the mice weresacrificed at 30 weeks of age. Sequential quantitation or IgG, IgA or IgM inserum and the isotypes specific for each of the bacterial strains or LPS administered was performed by ELISA. The incidence of immunofluorescence positivityfor glomerular IgA and C3 was 37-71 and 37-66.7%, respectively, in the IPgroups that had received bacterial cells of each strain, which was significantly higher than that in the IP groups given LPS or in the controls. These results suggest that cell wall components common among gram-negative bacteria, other than LPS, play a major role in the glomerular deposition of IgA and C3. This is the first use of gram-negative bacteria to establish an active model of IgA nephropathy.

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