Stage classification of IgG4-related dacryoadenitis and sialadenitis by the serum cytokine environment

<p><b>Objectives:</b> Patients with immunoglobulin-G4 related disease (IgG4-RD) diagnosed according to the comprehensive diagnostic criteria (CDC) show varied therapeutic responses and prognoses. We assumed that there are clinical stages in IgG4-RD and have verified it using serum cytokine levels in the groups classified by lesion distribution.</p> <p><b>Methods:</b> Definite IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) cases were divided according to the CDC for IgG4-RD into 11 cases with focal type and 30 cases with systemic type. The levels of serum interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, IL-15, IL-21, interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and monocyte chemotactic protein (MCP)-1 were measured in healthy controls, allergic patients, probable IgG4-RD cases, and focal and systemic type cases. The cytokine environment was analyzed in each group. The 52 definite IgG4-RD cases were next classified into four groups with cluster analysis in terms of therapeutic responses and prognosis. The relationships between each cytokine level and therapeutic responses were also analyzed.</p> <p><b>Results:</b> Both serum IL-5 and IFN-α concentrations were very low in healthy controls, but they increased in the allergic cases, probable cases, and focal and systemic type cases. The level of serum IL-5 was significantly higher in definite cases than in healthy controls. The serum IL-5 level was also significantly increased in the groups with a poor prognosis than in the good prognosis group.</p> <p><b>Conclusion:</b> These results suggest that there are clinical stages in IgG4-RD, and serum IL-5 play roles in the pathogenesis of IgG4-RD.</p

Pathological findings of the biopsies during lower gastrointestinal endoscopy in patients with acute gastrointestinal graft-versus-host disease or infectious colitis.

<p>Pathological findings of the biopsies during lower gastrointestinal endoscopy in patients with acute gastrointestinal graft-versus-host disease or infectious colitis.</p

Complications during or after the endoscopic procedures.

<p>Complications during or after the endoscopic procedures.</p

Backgrounds of 182 patients who underwent hematopoietic stem cell transplantation.

<p>Backgrounds of 182 patients who underwent hematopoietic stem cell transplantation.</p

Pathological findings.

<p>(a) Crypt cell apoptosis in patients with acute GI-GVHD, (b) Ductal atrophy in patients with acute GI-GVHD, (c) Inclusion body in patients with CMV infection.</p

Factors related to non-recurrence in the univariate or multivariate analysis.

<p>Factors related to non-recurrence in the univariate or multivariate analysis.</p

Schematic diagram of the patients enrollment in this study.

<p>Schematic diagram of the patients enrollment in this study.</p

Clinical course after the endoscopic procedures.

<p>Clinical course after the endoscopic procedures.</p

Patients’ characteristics and details of the endoscopic procedures.

<p>Patients’ characteristics and details of the endoscopic procedures.</p

Endoscopic findings.

<p>(a) tortoiseshell-like mucosal pattern in patients with acute GI-GVHD, (b) erosion/ulceration in patients with acute GI-GVHD, (c) redness in patients with infectious colitis.</p