Central MHC genes affect IgA levels in the human: reciprocal effects in IgA deficiency and IgA nephropathy.

This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA-B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a susceptibility locus in the central MHC. Provisional mapping within this region is discussed.

IgG4-related sclerosing disease of the small bowel presenting as necrotizing mesenteric arteritis and a solitary jejunal ulcer.

Since first described in the mid 1990s, there has been burgeoning literature on IgG4-related sclerosing disease. The number of sites that may be involved is ever increasing, with the pancreas, salivary glands, and lymph nodes being the most commonly affected organs. There are no well-documented cases arising in the gastrointestinal tract. In this report, we present the first case to our knowledge of IgG4-related sclerosing disease involving the small bowel with a distinctly unusual clinicopathologic presentation. A previously well 46-year-old woman presented with a 2-year history of intermittent abdominal pain with recent worsening due to small bowel obstruction. Following imaging, which showed jejunitis with surrounding mesenteric inflammatory changes, she proceeded to a segmental small bowel resection. The resected jejunum revealed an isolated, stenosing chronic ulcer associated with a necrotizing mesenteric arteritis. A transmural inflammatory infiltrate rich in IgG4 plasma cells was seen in the wall of the bowel and mesenteric artery. Abundant IgG4 interfollicular plasma cells were also identified in a mesenteric lymph node. The serum IgG4 level was elevated at >800 mg/dL (reference range 8 to 140 mg/dL). Although phlebitis is an almost constant feature of this disease, arteritis is not described other than in the lung and aorta. In this report, we also discuss the diagnostic pitfalls and the differential diagnoses that should be considered when this condition arises in the gastrointestinal tract.

Paraspinal and scapular myopathy associated with scleroderma.

OBJECTIVE: To describe a form of inflammatory myopathy with prominent involvement of the paraspinal and scapular muscles in patients with scleroderma. METHODS: Review of clinical records, laboratory investigations, and muscle biopsies. RESULTS: Patients presented with a "dropped head" resulting from weakness of the posterior cervical muscles (three cases) or camptocormia ("bent spine") resulting from weakness of the paraspinal muscles (two cases) and variable weakness and atrophy of shoulder girdle muscles with mild or absent pelvic girdle involvement. Biopsies from the deltoid or paraspinal muscles showed myositis of variable severity and scleroderma vasculopathy in all cases. The response to prednisolone and cytotoxic agents was poor, but there was a good response to intravenous immunoglobulin therapy in one case. CONCLUSIONS: Patients with scleroderma may develop a restricted form of immune-mediated inflammatory myopathy with a predilection for the paraspinal and scapular muscles, which is poorly responsive to treatment with glucocorticoids and immunosuppressive agents and may require consideration of other treatment modalities.