Autoimmune conditions seen in 1 in 10 IgG4-RD patients: Study

Nearly one in 10 people with immunoglobulin G4-related disease (IgG4-RD) also have at least one co-existing autoimmune disease, according to a real-world study in China.

Researchers identified 19 different autoimmune diseases in 85 IgG4-RD patients, most of which developed before or concurrently with the IgG4-RD diagnosis.

Even so, the long-term outcomes for IgG4-RD patients were positive, regardless of whether or not they had a co-existing autoimmune disease.

“IgG4-RD and [autoimmune diseases] are not entirely contrary in the diagnosis of IgG4-RD,” the researchers wrote.

The study, “IgG4-related disease with comorbid autoimmune diseases: a retrospective study from a large cohort,” was published in Clinical Rheumatology.

Autoimmune diseases often overlap

IgG4-RD is a chronic, immune-mediated condition in which certain immune cells, most commonly those producing the antibody IgG4, move into tissues, causing inflammation that can lead to scarring (fibrosis) and tumor-like masses in multiple organs.

“The [development] of IgG4-RD is associated with dysregulation of … immune responses, and multiple potential autoantigens have also been identified in this disease,” the researchers wrote. Autoantigens are molecules normally produced by the body but which are recognized as foreign by self-reactive antibodies in autoimmune diseases, triggering an immune response against them.

Because autoimmune diseases (AIDs) typically arise from an abnormally activated immune system, it’s common for two or more of these conditions to occur in a single person. However, while some researchers argue that IgG4-RD may be considered an AID, others believe that the disease’s features set it apart from common AIDs.

“Therefore, the relationship between IgG4-RD and AID is yet to be fully elucidated,” the researchers wrote.

Some studies have suggested that a small proportion of IgG4-RD patients have co-existing AIDs. A team of scientists in China previously discovered that about one in six IgG4-RD patients had a family history of AIDs, and those who did had earlier IgG4-RD onset and a higher rate of positive tests for a type of self-reactive antibodies called ANAs.

To investigate further, the same team retrospectively analyzed data from 879 adults newly diagnosed with IgG4-RD who were enrolled in an observational clinical trial (NCT01670695) in China. At the study’s start, none had received treatment for the disease.

About one in 10 (9.67%) had an AID. The most common were vitiligo (17.6%), followed by systemic vasculitis (14.1%), psoriasis (14.1%), Hashimoto’s thyroiditis (12.9%), and rheumatoid arthritis (11.8%). Most AIDs occurred before (59.4%) or at the same time (31.3%) as IgG4-RD.

Compared with Chinese and global populations, the prevalence of several AIDs was markedly higher in IgG4-RD patients: vitiligo (1.71% vs. 0.23%), rheumatoid arthritis (1.14% vs. 0.24%), primary biliary cholangitis (1.37% vs. 0.47%), and type 1 diabetes (0.8% vs. 0.09%).

“This selective susceptibility may suggest a shared potential [disease-causing] mechanism rather than coincidence,” the researchers wrote.

In the AID group, the organ most affected by IgG4-RD was the tear gland (47.1%), followed by the salivary gland (38.8%). In those without AIDs, it was the opposite: the salivary glands were most affected (58.7%), followed by the tear glands (51.9%). Pancreas and lymph node involvement were similar between the two groups.

“There was no significant difference in terms of family history of AIDs between [AID-positive] and [AID-negative] groups,” the researchers wrote.

In blood tests, more than twice as many IgG4-RD patients with AIDs tested positive for ANAs than those without AIDs (54.1% vs. 23.2%). They also had significantly lower blood levels of IgG4 and a higher erythrocyte sedimentation rate (ESR), a marker of body-wide inflammation.

A little more than half (55.3%) of the 85 IgG4-RD patients had body-wide AIDs, whereas the remaining (44.7%) had AIDs limited to particular tissues or organs.

While all groups had a median of three involved organs, IgG4-RD patients without AIDs were significantly more likely to have multi-organ involvement than those with body-wide AIDs. The body-wide AID group also had significantly higher ESR and IgG4 levels than those with organ-specific AIDs, with ANA levels predominant in both groups.

Regarding treatment, the initial glucocorticoid dose was similar across all groups. The treatment regimen consisted predominantly of glucocorticoids combined with immunosuppressants, followed by glucocorticoids alone, and then glucocorticoid-sparing therapy.

Over a median follow-up of 43 months (about 3.6 years), the proportion of patients with or without AIDs who experienced a recurrence of IgG4-RD was similar (35.8% vs. 37.5%). No differences were seen between groups in relapse-free survival, or the time alive without a relapse. Relapse and survival outcomes were also similar between those with body-wide or organ-specific AID involvement.

“The long-term prognosis of patients was favorable, regardless of whether they had comorbid AID,” the team wrote. “In the future, further research is needed to understand the intrinsic connection between AIDs and IgG4-RD.”