Disease symptoms in AAV vary by age at diagnosis, sex, study finds
Newly ID'd patient subgroups, by ANCA type, may help improve treatment
Disease symptoms among people with ANCA-associated vasculitis (AAV) were found to vary by age at diagnosis and biological sex, according to data from more than 1,100 Scandinavian patients.
“We identified significant differences in clinical presentation of the disease between female and male patients and between patients with a young age at diagnosis … versus patients with an older age,” the researchers wrote.
By analyzing the data with the help of computer algorithms, the researchers also distinguished several patient subgroups based on type of ANCAs — the self-reactive antibodies that drive most AAV cases — and organ involvement.
“These findings may facilitate the prediction of organ involvements in patients with AAVs in the clinical setting,” the team wrote.
The study, “In-Depth Analysis of Disease Manifestations in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides Identifies Distinct Clinical Phenotypes,” was published in Open Rheumatology, a journal of the American Academy of Rheumatology.
Significant differences seen in disease symptoms in males vs. females
AAV is an autoimmune disease marked by inflammation in small blood vessels. Most cases are associated with the production of ANCAs that target one of two enzymes: proteinase 3, called PR3, or myeloperoxidase, known as MPO.
Blood vessel inflammation in AAV can cause damage to many different organ systems throughout the body; as such, symptoms and manifestations of the disease can vary widely from person to person. In addition, some research has suggested that AAV manifestations may vary by sex and age.
“The [variability] of the AAVs in terms of organ involvement and prognosis is a significant obstacle in the clinical follow-up of patients with AAVs,” the researchers wrote.
Now, a team led by scientists in Sweden analyzed data from 1,156 people with AAV in an attempt to identify and characterize subgroups of patients. The researchers’ focus was on AAV type, ANCA type, sex of the patient, age at diagnosis, and organ involvement.
All of the patients, the researchers found, had been diagnosed with one of the two most common types of AAV: granulomatosis with polyangiitis, known as GPA, seen in 80%, or microscopic polyangiitis, called MPA, found for 20%.
The results showed that, among GPA patients, males were significantly more likely to be positive for anti-PR3 ANCAs, while females were more commonly positive for anti-MPO ANCAs. Male GPA patients also were significantly more likely to have kidney or lung disease than their female counterparts.
Analyses based on age at diagnosis showed that GPA patients diagnosed before age 32 were significantly more likely to be female and to have disease involvement affecting the ears, nose, and/or throat (ENT).
By contrast, GPA patients who were diagnosed later in life were significantly more likely to experience peripheral nervous system involvement. The peripheral nervous system refers to the network of nerves outside the central nervous system, or CNS, which comprises the brain and spinal cord.
Disease relapses, when symptoms suddenly worsen, were significantly more frequent among GPA patients than those with MPA. Among GPA patients, a diagnosis before 32 years of age and lung involvement were also significantly associated with a higher chance of relapse.
The risk of relapse in MPA patients was increased among those who had muscle and/or skeleton involvement as part of their disease.
Computer analysis IDs 5 patient subgroups in GPA, 7 in MPA
The researchers then conducted clustering analyses — meaning they used computer algorithms to group patients with similar disease characteristics.
That analysis identified five subgroups among GPA patients. The largest was characterized by the presence of anti-PR3 ANCAs plus ENT involvement, and the second largest by the presence of anti-MPO ANCAs.
“These two clusters [subgroups] also largely overlap the clinical diagnoses GPA and MPA, respectively, confirming the well-established categorization of AAVs into either PR3-ANCA/MPO-ANCA positive disease or GPA/MPA,” the team wrote.
The other three GPA subgroups were defined by gastrointestinal, heart, or CNS involvement.
Among MPA patients, the analysis identified seven subgroups. The largest was defined by the presence of anti-MPO ANCAs plus kidney involvement, while the second largest subgroup was marked by ANCAs against PR3.
The remaining five subgroups each had a maximum of 11 patients — likely affected by the smaller number of people with MPA in the study, per the researchers. Three of these subgroups were again marked by heart, CNS, and gastrointestinal involvement. One of the others was characterized by no kidney involvement, while another subgroup was marked by eye involvement.
We have identified clinically relevant subgroups of patients with AAVs, defined by sex, ANCA, age at diagnosis, and organ system involvement. … The results of this study and future work will help to individualize and improve treatment and care of patients with AAVs.
“PR3-/MPO-ANCA defined the largest clusters, whereas heart, gastrointestinal, and central nervous system involvement were hallmarks for three clusters for both patients with GPA and MPA,” the researchers wrote.
The team also found other notable trends: For one, AAV patients with lung involvement also frequently had heart involvement. In GPA patients, meanwhile, gastrointestinal involvement tended to co-occur with skin involvement, and eye involvement often occurred alongside CNS involvement.
“We have identified clinically relevant subgroups of patients with AAVs, defined by sex, ANCA, age at diagnosis, and organ system involvement,” the team wrote, noting their work may help in predicting organ involvement among AAV patients by clinicians.
Further research is needed to evaluate simultaneous health conditions, treatment effects, and clinical outcomes in these distinct subgroups, the researchers noted.
“The results of this study and future work will help to individualize and improve treatment and care of patients with AAVs,” they concluded.
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