Background/Purpose

IgG4-related disease (IgG4-RD) has emerged as an immune-mediated disease that links multiple fibro-inflammatory conditions through common pathology and pathophysiologic mechanisms.  Most of the literature on IgG4-RD is comprised of case reports and small case series focused on individual organ manifestations.  We report detailed clinical features of the first 100 patients with IgG4-RD evaluated at our center. 

Methods

We reviewed the cases of the first 100 patients included in a database maintained by the Massachusetts General Hospital Center for IgG4-RD.  All patients had biopsy-proven disease and 75 were on no immunosuppression at the time of evaluation yet had active disease.  Clinical and laboratory data were extracted from the electronic medical record.  An IgG4-RD responder index score > 3 defined active disease. Serum IgG4 concentrations were determined by nephelometry after serial dilution to prevent the prozone effect.  Circulating plasmablasts and SLAMF7+ CD4+T cells were measured by flow cytometry.

Results

The average ages at evaluation and disease onset were 55 years (range: 24-83) and 49.9 years (range: 12-82), respectively.  The majority of patients were white (75%) and male (63%); the mean number of organs affected was 2.8 (range 1-7). The most commonly involved organs were the submandibular glands, orbit, lymph nodes, pancreas, and retroperitoneum; fifty-five patients had sustained permanent damage due to IgG4-RD (Table 1).  

Forty-seven patients had received glucocorticoid therapy and all had either failed treatment or required ongoing treatment to maintain disease control.  Only 38 (53%) of the 75 patients on no treatment at baseline had an elevated serum IgG4 concentration.  Elevated serum IgG4 levels correlated with an inflammatory phenotype (increased acute phase reactants) and multi-organ disease.  Regardless of the serum IgG4 concentrations, patients had elevated levels of circulating SLAMF7+ CD4+ T cells and plasmablasts.  Male patients had a higher average serum IgG4 concentration (597mg/dL versus 233mg/dL; P=0.03) but neither the proportion with an elevated baseline value nor the number of organs involved differed.  Patients with renal disease, lymphadenopathy, and retroperitoneal fibrosis represented distinctive subtypes on the basis of complement levels, serum IgG4 concentrations, number of organs involved, and inflammatory markers.      

Conclusion

We report the baseline features of our first 100 patients with biopsy-proven IgG4-RD.  The majority of the patients were on no treatment at the initial assessment, permitting insights into the pre-treatment features of IgG4-RD.  Our study stands in contrast to all IgG4-RD publications to date as this is the first study to describe the clinical and laboratory features of a large, diverse cohort with IgG4-RD. 

Table 1: Organ Involvement and Damage

Organ Involvement
	# of cases		# of Cases
CNS	3	Aorta	9
Orbit	25	Heart	1
Parotid	15	Retroperitoneal fibrosis	19
Submandibular	29	Sclerosing mediastinitis	2
Mastoid	1	Sclerosing mesenteritis	1
Nasal Cavity	2	Pancreas	22
Sinusitis	5	Liver	3
Tonsilitis	1	Bile duct	8
Other ENT	6	Gallbladder	1
Thyroid	5	Skin	2
Lymph nodes	24	Prostate	3
Lung	16	Other	5
Kidney	8
Damage
Biliary	3	Pancreas	8
Nasal Septum	2	Kidney	8
Submandibular Gland	9	Lung	8
Sinus	4	Ureter	4
Palate	2	Vascular/SVC Syndrome	2
Thyroid	3	Chronic Pain	3
Aorta	2	Coronary	2
Other	9

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/igg4-related-disease-baseline-features-in-100-patients-with-biopsy-proven-disease/