Low immune cell count linked to higher risk of infection in MPA

Severe infections found to be a risk for older adults in new study

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Lower-than-normal counts of lymphocytes, a type of immune cell, are linked to a higher risk of severe infection in older adults with microscopic polyangiitis (MPA), the most common type of ANCA-associated vasculitis (AAV), according to a new Japanese study.

In fact, the study found that “56 severe infectious episodes occurred in 51 patients (39.2%)” during a follow-up period of just longer than three years, with older age identified as one of the key “significant predictors of severe infection,” the researchers noted.

These findings highlight the need for physicians to “closely follow up older adults with MPA and evaluate lymphocyte counts to monitor the development of infections,” the team wrote.

The study, “Lymphopenia is a risk factor for severe infections in older patients with microscopic polyangiitis: a retrospective cohort study in Japan,” was published in the journal Rheumatology Advances in Practice.

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AAV is a group of disorders characterized by inflammation and damage to small blood vessels that can affect the function of several organs, including the kidneys and the lungs. The inflammation is usually caused by ANCAs, which are self-reactive antibodies that target one of two proteins — PR3 or MPO — in neutrophils, a type of immune cell.

“Although recent advances in immunosuppressive treatments have improved the prognosis of AAV, infections remain a major contributor to the mortality of patients with AAV infections remain a major contributor to the mortality of patients with AAV,” the researchers wrote.

In a previous study, lymphopenia, or low lymphocyte counts, was shown to be a risk factor for infection requiring hospitalization in AAV patients. However, this study included mostly middle-aged people with granulomatosis with polyangiitis, which is another type of AAV.

“Therefore, it is not clear whether the results will be applicable to older patients with MPA, who exhibit the most common form of AAV,” the researchers wrote.

To answer this, a team led by researchers at the Aichi Medical University, in Japan, looked back at data from 130 MPA patients with a median age of 75. All were diagnosed at their institution between 2004 and 2019.

These patients — 70 men and 60 women — were followed for a median of 38 months, or a little more than three years. All had received immunosuppressive treatment and had data on glucocorticoid use during follow-up.

All but one patient tested positive for ANCAs against MPO — the most common type in MPA — while the remaining patient had anti-PR3 ANCAs. Most patients (91.5%) had kidney involvement, and nearly a third (31.5%) had lung involvement.

Half of the patients received methylprednisolone pulse therapy as induction treatment. During follow-up, 69 patients (53.1%) received immunosuppressive medications, including cyclophosphamide, rituximab (sold as Rituxan in the U.S. and MabThera in Europe), azathioprine, and mizoribine.

A total of 126 patients (95.4%) received and continued preventive antibiotic therapy during immunosuppressive treatment. The remaining patients discontinued the preventive medication due to allergic reactions or low platelet counts.

Lymphopenia was defined as an absolute lymphocyte count below 1,000 cells per microliter (mcl), and further subdivided into severe (below 500 cells/mcl) and moderate (between 500–1,000 cells/mcl).

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Lymphopenia now found to be strongest risk factor for infection in MPA

With those guidelines, the researchers then analyzed the number of patients who developed any severe infection requiring hospitalization for any cause during follow-up and whether such infections were preceded by lymphopenia.

A total of 51 patients (39.2%) developed at least one severe infection, while 79 did not. Patients with severe infections were significantly older (median of 78 vs. 72 years) and were significantly more likely to show lung involvement (51% vs. 19%) than those in the non-infection group.

A significantly greater proportion of patients in the severe infection group received methylprednisolone pulse therapy relative to those in the non-infection group (72.6% vs. 35.4%).

Patients who developed severe infections also showed a tendency for worse kidney function, but group differences in a validated measure of kidney function, called the glomerular filtration rate, did not reach statistical significance.

Most patients (85.4%) achieved remission, defined as the absence of clinical signs and symptoms of active blood vessel inflammation after six months of treatment. However, the disease relapsed in about a third of them (35.4%). A total of 27 patients developed kidney failure and required permanent dialysis (20.8%).

While there were no significant group differences in terms of these outcomes, a significantly higher proportion of patients in the severe infection group died during follow-up (41.2% vs. 13.9%). Infection was the most common cause of death in these patients (85.7%), while patients in the non-infectious group died of several other causes.

Patients with a severe infection had significantly lower lymphocyte counts during follow-up than those without a severe infection, despite showing no differences in counts at the start of the study, immunosuppressive therapy, or glucocorticoid dose course.

These results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.


Statistical analyses accounting for multiple variables showed that older age, methylprednisolone pulse therapy, and moderate and severe lymphopenia were all significant predictors of severe infection.

Lymphopenia was the strongest risk factor, with moderate lymphopenia being associated with a seven times higher risk of severe infection, and severe lymphopenia with a 36 times increased risk.

Further analysis confirmed that occurrence of severe infection was significantly higher in patients with severe lymphopenia.

Overall, these findings point to “lymphopenia as a significant predictor of the risk of severe infection in older adults with MPA,” the researchers wrote

The team added that “these results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.”

Still, larger studies, involving patients from several regions, are needed to confirm these findings, the team noted.