Four distinct IgG4-related disease groups described in study

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603