Monoclonal gammopathy of undetermined significance in Chinese population: A prospective epidemiological study

Abstract The aim of this study was to identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in different groups of age and the clinical features in China. This multicenter prospective study enrolled 1797 health subjects. The overall prevalence of MGUS was 2.73%. The prevalence of different age groups was 1.19% (41‐50 y), 1.16% (51‐60 y), 2.19% (61‐70 y), 3.66% (71‐80 y), and 7.76% (≥81 y). The prevalence of MGUS in male (n = 843) was 2.97%, while the prevalence of MGUS in female (n = 952) was 2.52%, but this difference of the two groups was not statistically significant. As for subtype of MGUS, IgG subtype was 55.1% (27 cases), IgA subtype was 14.3%, and IgM subtype was 12.2%. The M protein of one case became negative after 3 months, and the others remained positive without obvious disease transformation (follow‐up duration: 3‐7 mo). Thus, the prevalence of MGUS in China was similar to that in Mexican Americans, but lower than that in the other Asian country, American Whites, American Blacks, and Africans, and had a trend of increase with age. Male had higher prevalence of MGUS in China. The most common subtype was IgG.

mosome G-banding), imaging test (ie, cranial pelvis X-ray, cervical, thoracic, and lumbosacral vertebral magnetic resonance imaging or PET-CT). Subjects with MM, amyloidosis, POEMS, and lymphoma were excluded. Once subjects were diagnosed as MGUS, they were followed up and examined with blood and urine tests once every 3 months as well as bone marrow puncture once every year. Subsequent follow-up duration could be extended to 6 months if the M protein was unchanged within 1 year (ie, 10%). If the disease progression was identified in subjects, it should be registered and reported. Imaging examinations were conducted if necessary based on the decision of researchers. Therefore, capillary electrophoresis was used for follow-up screening.

| Follow-up
The M protein of one case became negative after 3 months, and the others remained positive without obvious disease transformation (follow-up duration: 3-7 mo).

| DISCUSSION
Patients with MGUS were always asymptomatic, and the majority of patients were identified with the change of immunoglobulin at annual physical examination or visit due to other illnesses and then diagnosed based on serum protein electrophoresis, serum immunofixation electrophoresis, and free light chain. Since the false dismissal rate was high, MGUS can be easily ignored by the clinicians. Therefore, the actual rate of MGUS was much higher than the data. The positive rate was different by different detection methods. In a large study in Olmsted County, Kyle and his colleagues analyzed more than 75% of residents (50 y or older), using agarose gel electrophoresis test, and identified 3.2% of subjects with MGUS. There was a significant age-dependent increase with the prevalence among persons aged 70 years or older (up to 5.3%). 7 Subsequently, Dispenzieri and his colleagues used the free light-chain assay on a majority of the same people and showed a higher prevalence of MGUS in people aged more than 50 (4.2%). 8 An Italian study 19 by means of capillary electrophoresis showed that the prevalence of MGUS increased from 3.2% to 6%, which nearly doubled than that previous report. Our study used capillary electrophoresis and found that the prevalence of MGUS over 40 years old was 2.73%, which was lower than that in Italy. This may be related to ethnic differences.
Our data also verified that the men had a higher prevalence (2.97%-2.52%) in China, which was consistent with previous report in the United States (2.8%-2.0%). 2 The data from Mayo Clinic showed that the most common subtype of MGUS was IgG (69%), followed by IgM type (17%) and IgA type (11%). 7 However, the IgA type in Korea 18 was the most common subtype (43%), followed by IgG (29%) and IgM (19%). Our data were similar to that of Mayo Clinic, which showed that the most common subtype of IgG was 55.1%, but followed by IgA type (14.3%). Due to the heavy air pollution in China, there may be different types of distribution, such as the IgA type, which was slightly higher than that in Europe and the United States. The prevalence of IgA nephropathy in China is significantly higher than that of other countries, which may  20 Our study showed that the IgM type was 12.2%, which was lower than that of other countries without significant descending.
There were fewer plasma cells and lower cell proliferation in bone marrow of MGUS; hence, the conventional karyotype analysis was always normal in majority of patients. However, with the emergence of the more sensitive methods, people found that the incidence of chromosomal abnormalities was not uncommon. Bacher  Other studies also found that 12% to 17% of patients had progression at the 10 years of follow-up followed by 25% to 34% of progression in 20 years. [25][26][27] In our study, the follow-up duration was short without progression, but the monoclonal immunoglobulin of one case was missing during follow-up period.
Further study with longer follow-up time was still warrant to examine MGUS.
In conclusion, the prevalence of MGUS in China was similar to that in Mexican Americans, but lower than that in the other Asian country, American whites, American blacks, and Africans, which had a trend of increase with age. Male had higher prevalence of MGUS in China. The most common subtype was IgG. With the gradual increase of life expectancy in China, the screening and regular monitoring of MGUS were relevant.